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Flashcards in WBC Hematopathology Part 2 Deck (188):
1

Peripheral T-cell tumors are what % of NHL's in US and Asia?

5-10%

2

Peripheral T cell and NK cell tumors are most common where?

In Far East

3

How do nodes appear in peripheral T cell neoplasms?

Diffuse effacement of nodal architecture

4

Markers for T-cell neoplasms? 2

1. Pan-T Markers (CD2/3/5)
2. CD4 or CD8 possibly

5

What defines a T-cell malignancy?

Clonal T-cell receptor gene rearrangements

6

How do T cell neoplasms generally present? (5)

Disseminated adenopathy
Eosinophilia
pruritis
Fever
Weight loss

7

How do T cell neoplasms respond to therapy?

Respond poorly due to being so aggressive

8

5 Peripheral T cell neoplasms?

1. Anaplastic large cell lymphoma
2. Adult T-cell leukemia/Lymphoma
3. Mycosis Fungoides and Sezary Syndrome
4. Large Granular Lymphocytic Leukemia
5. Extranodal NK/T-Cell lymphoma

9

Anaplastic Large Cell lymphoma has what rearrangement?
This produces what?

Rearrangement of ALK gene on chromosome 2p23
Active tyrosine kinases

10

What is the hallmark cell in Anaplastic Large Cell lymphoma

Large, anaplastic cells

11

What does Anaplastic Large Cell lymphoma's lymph node pattern mimic? (2)

1. Metastatic carcinoma
2. Hodgkin lymphoma variants

12

Anaplastic Large Cell lymphoma with ALK rearrangement are seen in what population?
What is prognosis?

Kids
Good prognosis

13

Anaplastic Large Cell lymphoma without ALK rearrangement is seen in what population?
What is prognosis?

Older adults
Worse prognosis

14

Adult T-cell leukemia/lymphoma is seen in adults infected with what?

Retrovirus HTLV-1

15

Where is HTLV-1 seen in the world? 3

Japan
West Africa
Caribbean

16

Clinical findings in Adult T-cell leukemia/lymphoma? 4

1. Skin lesions
2. Hypercalcemia
3. Hepatosplenomegaly
4. Elevated WBC count with multilobulated CD4's

17

Prognosis of Adult T-cell leukemia/lymphoma?

Less than a year, extremely aggressive

18

Mycosis Fungoides and Sezary syndrome are two manifestations of what?

What are the hallmark cells involved?

Cutaneous T-cell lymphoma

Peripheral CD4 T cells wth a crebriform appearance

19

How does Mycosis FUnoides present as?
Where do the T cells go?

Inflammatory pre-mycotic phase and progresses through a plaque phase to a tumor phase.

infiltrate skin

20

Sezary syndrome has what main presentation?

What is prognosis?

Generalized exfoliative erythroderma

Incurable but long survival

21

Large granular lymphocytic leukemia is seen how?
What population mainly has it?
What organs does it avoid?

With granules which is strange for lymphocytes

Adults

Lymph nodes and liver

22

Hallmark of Large granular lymphocytic leukemia?

Lymphocytes in peripheral blood and BM with blue cytoplasm and scattered azurophilic granules

23

Two symptoms of Large granular lymphocytic leukemia?

Neutropenia
Anemia

24

Two variants of Large granular lymphocytic leukemia
Which is more severe?
Which has splenomegaly and lymphocytosis?

T cell: Mild/Lymphocytosis + Splenomegaly

NK Cell: Aggressive

25

What are the five subtypes of hodgkin lymphomas?

– Nodular sclerosis
– Mixed cellularity
– Lymphocyte-rich
– Lymphocyte depletion (rare)
– Lymphocyte predominance (LP)

26

Which of the hodgkin subtypes are classical hodgkin lymphoma?

First four (not LP) since the R-S cells have similar immunophenotype

27

What makes LP different from other hodgkin subtypes?

Malignant cells express a different B-cell phenotype (CD20, CD15 and CD30 -)

28

Hodgkin lymphoma neoplasm is located where in body?
What virus causes some of these?
Prognosis
Best prognosis indicator?

Germinal center or post-germinal center B lymphocytes

EBV

Very good

Clinical stage is great indicator

29

Side effects of chemo/radiotherapy against Hodgkin lymphoma?

1. Myelodysplasia
2. Acute leukemia
3. Lung cancer
4. Melanoma
5. breast cancer
6. Gastric cancer
7. NHL

30

How does one avoid the cancers caused by chemo and radiotherapy?

Use new drug combinations and less of the drugs

31

What is Stage I Hodgkin?

Involvement of single lymph node region or single extra-nodal site

32

Stage II hodgkin?

Two or more lymph node regions (or extranodal sites) on same side of diagphragm

33

Stage III Hodgkin's

Involvement of lymph node regions on both sides of the diaphragm.
May include spleen or localized extranodal disease

34

Stage IV Hodgkin's

Diffuse extralymphatic disease in liver BM, lung, skin

35

Most common Hodgkin subtype?

Nodular sclerosis

36

Nodular sclersosis is what % of HL?
Difference in sexes?

65-70%

Sexes are equal

37

What are the two histo signs of nodular sclerosis?

Lacunar cells
Bands of collagen fibrosis

38

R-S cells in nodular sclerosis have what markers?

1. Positive for CD15 and CD30
2. Negative for CD45 and other B and T markers

39

Age of nodular sclerosis patients?

1. young adults

40

Mixed cellularity hodgkin lymphoma is the most common form of HL in what group of patients?
Sex difference?

Males older than 50

41

Immunophenotype of mixed cellularity hodgkin?

Same as Nodular
1. Positive for CD15 and CD30
2. Negative for CD45 and other B and T markers

42

Patients with mixed cellularity hodgkin are more likely to present how?
Prognosis

Advanced disseminated disease

Prognosis remains really good

43

RS cells in mixed cellularity hodgkin contain what at 70%?

EBV

44

Lymphocyte-Rich hodgkin lymphoma has what cell predominate?

Reactive lymphocytes

45

How to distinguish between Lymphocyte Rich and Lymphocyte Predominance?

Lymphocyte Rich has frequent mononuclear R-S cells of characteristic HL immunophenotype

46

Lymphocyte-Rich hodgkin lymphoma is associated with what virus at 40%

EBV

47

Prognosis of Lymphocyte-Rich HL?

Very good to excellent prognosis

48

What is the least common form of hodgkin lymphoma?

Lymphocyte Depletion

49

What cells are low in Lymphocyte-Depletion?
Which are high?
What is immunotype for these cells?

Few lymphocytes

Abudant R-S cell variants

HL immunotype

50

Age and patient group of Lymphocyte depletion HL?

Elderly

HIV-positive

51

EBV positive in what % of Lymphocyte depletion HL?

90%

52

What is prognosis in Lymphocyte depletion HL?

Less favorable

53

Lymphocyte predominance HL is what patient group?

Males younger than 35

54

Lymphocyte predominance HL is characterized by what cells?
Other cells (2)

Lymphohistiocytic variant cells/Popcorn cells

Reactive lymphocytes and histiocytes

55

Are RS cells present in Lymphocyte predominance HL?

Yes, but very rare

56

L and H cells have what markers? (4)

What does this mean?

1. Positive for CD20 and BCL6 (b cell lymphoma characteristic)
2. Negative for CD15 and CD30 (RS cells)

This is really a B-cell lymphoma

57

Is LP associated with EBV?

No

58

three major categories of myeloid neoplasms?

Acute myeloid leukemias
Myelodysplastic Syndromes
Myeloproliferative disorders

59

What is AML?

blockage in differentiation of early myeloid cells which causes blasts to accumulate in BM and then circulate in peripheral blood

60

What is Myelodysplastic syndrome?

Terminal differentiation of early myeloid cells occurs but is disordered and ineffective

61

How is MDS marked?

Presence of dysplastic marrow precursors and peripheral blood cytopenias

62

What is a myeloproliferative disorder?

Neoplastic clone retains capacity to undergo terminal differentiation with dysregulated goal.

63

Myeloproliferative disorders result in what peripheral blood?

Increased RBC's, WBC's and platelets

64

Acute myeloid leukemia is due to what?

Acquired oncogenic mutation blocking normal cell differentiation --> Accumulation of myeloblasts in marrow

65

AML leads to what?
Which appears how (3)

Marrow failure

Anemia, thrombocytopenia, neutropenia

66

Acute Myeloid Leukemia occurs when?
What age most?

All ages

Peaks after 60

67

Acute myeloid leukemia signs and symptoms resemble what?
Related to what?

Acute lymphoblastic leukemia

Splenomegaly and lymphadenopathy

68

How might AML rarely prsent?

Infiltration of what suggests monocytic types?

Discrete tissue mass like a sarcoma or myeloid tumor

Infiltration of skin and gingiva

69

Diagnosis of AML
What is done first?
What is the key diagnostic finding?

Karyotypic findings
Greater than 20% myeloblasts in BM

70

Cytogenetic abberations in AML? (2)

1. Disrupt genes encoding TF's for normal differentiation
2. Activate mutated tyrosine kinases --> Constant proliferation signals

71

The M3 AML affects what population most?
What does it progresss to?
Chromosomal abnormality?
Genes involved?

Younger people

DIC

t(15;17)(q22:q21)

PMU/RARA

72

What stains do you do for AML? 3

1. Myeloperoxidase (myelocytic)
2. Specific esterase (myelocytic)
3. Nonspecific esterase (monocytic)

73

Markers of AML? 4

CD13
CD14
CD15
CD33

74

What are the WHO classifications of AML? 4

1. AML with particular genetic abnormalities
2. AML with MDS-like features
3. AML, therapy related
4. AML not otherwise specified

75

AML has what particular genetic abnormalities?

t(8;21)
inv(16)
t(15;17)

76

Using FAB classification, which AML's are precursor of neutrophils?

M0 through M3

77

Using FAB classification, which AML has both myeloid and monocytic precursors?

M4 and M4 eos

78

Under FAB classification, which AML's are precursors of different things?

M5: Monocytic
M6: Erythroid
M7: Acute megakaryocytic

79

AML prognosis?

Chemo can get you into complete remission but 5 year survival is low.

80

High risk forms of AML and relapsing AML are treated with what?

BM transplant

81

Main histo findings of AML? 2

Myeloblasts
Auer rods

82

Acute promyelocytic leukemia (APL/AML-M3) exhibits what genetic mutation?

t(15;17)

83

What protein forms in APL/M3?

Fusion of retinoic acid receptor alpha (RARA) and PML gene to make a product that blocks myeloid maturation at promyelocyte stage

84

How to overcome RARA-PML block in APL?

Vitamin A derivatives and chemo

85

APL is associated with what two things

DIC
Bleeding diatheses

86

What is the key cell finding in AML?

Auer rods in a Faggot cell

87

What is cause of most myelodysplastic syndromes?

Idiopathic/primary

88

What is identified in 70% of myelodysplastic syndromes?

Clonal chromosome abnormality in chromosomes 5, 7, 8, 20

89

What is the mean age of onset of myelodysplastic syndromes

70

90

Symptoms of myelodysplastic syndromes appear similar to what?

Pancytopenia: Infeciton, anemia, hemorrhage

91

What are the subtypes of myelodysplastic syndromes classified based on? 3

1. Number of blasts
2. cell lines
3. Presence of ring sideroblasts

92

What must be excluded before a diagnosis of myelodysplastic syndromes can be made?

All non-clonal causes for dysplasia must be disproved such as drugs, growth factor therapy, virus, immune disorder, vitamin deficient, too much zinc

93

How do myelodysplastic syndromes respond to therapy?

Poorly, but some may live more than 5 years.

94

What do younger patients with myelodysplastic syndromes get for treatment?

BM transplant

95

what is main cause of death in myelodysplastic syndromes?

Marrow failure: Thrombocytopenia and neutropenia

96

Myeloproliferative disorders have what mutation?
2 examples

Mutated tyrosine kinases causing GF-independent proliferation

1. BCR-ABL
2. JAK2

97

What are four features of myeloproliferative disorders?

1. Increased marrow proliferation (RBC, WBC, PLT)
2. Neopalstic stem cells seed secondary hematopoietic organs (hepatosplenomegaly)
3. Variable transofrmation to a spent phase with marrow fibrosis and peripheral cytopenis
4. Variable transformation to acute leukemias

98

Four main forms of myeloproliferative disorders?

1. Chronic Myeloid leukemia
2. Polycythemia Vera
3. Essential thrombocytosis
4. Primary myelofibrosis

99

Chronic myeloid leukemia affects what age mainly?

40-60 adults

100

What is main physical symptom of CML?

Splenomegaly

101

WBC count in CML?
Other cells present (2)

Over a 100,000

Eosinophils and basophils

102

CML has what % blasts?
What does bone marrow show?
What is the Leukocyte Alkaline Phosphatase (LAP) score?
Prognosis?

less than 10%

Panhyperplasia

Decreased leukocyte alkaline phosphatase score

Untreated survival of 3 years

103

50% of CML patients enter what phase?
what does this entail (4)

Accelerated phase

1. increasing anemia
2. Thrombocytopenia
3. More mutations
4. Blast crisis eventually

104

50% of CML patients enter wha tother phase?

There is a 30:70 ratio of what?

Blast crisis

30% are B cell ALL and 70% are AML

105

Treatment for CML?

Gleevec inhibits BCR-ABL fusion product of the mutated tyrosine kinase gene t(9;22)

106

What % get remission with Gleevec in CML?

90%

107

What is treatment of choice in younger CML patients?

BM transplant

108

Define polycythemia

Increase in concentration of erythrocytes in the blood

109

2 forms of polycythemia

1. Relative polycythemia
2. Absolute polycythemia

110

What changes in relative polycythemia?

Increase in hematocrit due to a decrease in plasma volume.
NO CHANGE IN TOTAL RBC mass

111

Causes of relative polycythemia (2)

1. Diminished plasma volume due to shock
2. Stress polycythemia

112

Absolute polycythemia is due to what?

Increase in total red cell mass

113

Two types of absolute polycythemia

Primary
Secondary

114

Primary polycythemia is characterized by what

Low EPO

115

Secondary polycythemia is characterized by what?

High or normal EPO

116

Appropriate EPO production occurs when?

Hypoxia and arterial O2 desaturation (high altitude, smoker, methemoglobinemia,)

117

Inappropriate EPO production occurs when (2)

1. Neoplasms
2. Renal pathology

118

Polycythemia Vera has signs and symptoms due to what?

EPO-independent increase in RBC mass

119

Polycythemia has strong association with what mutation?

JAK2

120

Increased blood volume and viscosity are due to what in polycythemia vera?

Increase in RBC cell mass

121

Polycythemia
HCT:
WBC:
PLT:
Basophils:

HCT = Over 60%
WBC: = High
PLT = High
Basophils = High

122

6 main signs of polycythemia vera?

1. Mild hepatosplenomegaly
2. Panhyperplasia and Decreased Iron
3. Plethora (ruddy red complexion)
4. Cyanosis
5. Intense pruritis
6. Major bleeding and thrombotic episodes

123

Polycythemia vera has an age of what?

60 years old

124

Death of polycythemia?

Bleeding or thrombosis

125

RBC mass in polycythemia vera can be kept maintained by what?

Phlebotomies

126

After 10 years what happens to Polycythemia vera patients?

Transition into spent phase with extramedullary hematopoiesis and splenomegaly

127

Major criteria for polycythemia vera? (2)
Minor criteria (2)

1. Elevated Hb
2. Presence of JAK2 mutation

1. BM biopsy showing hypercellularity with trilineage growth
2. Serum EPO decreased
3. Endogenous erythroid colony formation in vitro

128

Essential thrombocytosis is an increase in proliferation confined to what elements?

Megakaryocytic elements (platelets)

129

Diagnosis of essential thrombocytosis is described how?

Diagnosis of exclusion since all myelo-proliferative disorders can be associated with thrombocytosis

130

PLT count in essential thrombocytosis?

Greater than 600,000

131

Bone marrow of essential thrombocytosis appears how?

Hypercellular with increased abnormal megakaryocytes

132

Platelets appear how in essential thrombocytosis?

Enlarged and functionally abnormal

133

50% of essential thrombocytosis is associated with what mutation?

JAK2

134

Course of essential thrombocytosis?

Long asymptomatic periods with occaisional thrombotic or hemorrhagic crises

135

Two progressions of essential thrombocytosis?

1. Spent phase of myelofibrosis
2. Transform to AML

136

Survival of essential thrombocytosis?

12-15 years

137

Primary myelofibrosis has its fibrosis occur where early?

Marrow

138

Marrow fibrosis has what effect on body?

Suppress hematopoiesis --> pancytopenias --> Spleen and liver respond --> Extreme hepatosplenomegaly

139

What cell type increases and appears strange in primary myelofibrosis?
What does this stimulate?

Megakaryocytes

Stimualtes benign fibroblasts to lay down collagen and form marrow fibrosis

140

What mutation is in 50-60% of primary myelofibrosis?

JAK2

141

Peripheral blood in primary myelofibrosis demonstrates what? 2

Leukoerythroblastosis and Teardrop cells

142

Primary myelofibrosis appears in what age?
4 symptoms to present with?

older than 60

1. Anemia
2. Splenomegaly
3. Fibrosis
4. Gout

143

Cell changes in Primary myelofibrosis? 4

1. Increase basophils
2. Abnormal platelet morphology
3. Increased abnormal megakaryocytes
4. Marked marrow fibrosis

144

Survival length in Primary myelofibrosis?

3-5 years

145

Langerhans Cell histiocytosis is what?

Clonal proliferation of dendritic antigen-presenting cells normally found in many organs

146

What do cells contain in Langerhans Cell histiocytosis?

Markers (2)

Birbeck granules

S-100 and CD1a antigens

147

Old name for Langerhans Cell histiocytosis?

Histiocytosis X

148

Three entities of Langerhans Cell histiocytosis?

Multifocal multisystem LCH
Unifcoal and multifocal unisystem LCH
Pulmonary LCH

149

Multifocal multisystem LCH occurs when in life?
Main cell and its appearance?
Prognosis?

Before age 2

Monocytic cell with convoluted/folded nucleus

Agressive and fatal if untreated. Chemo can keep you alive

150

Unifocal and multifocal unisystem LCH involves what action?

Erosive accumulations of Langerhans cells in medullary cavities of bones

151

What bones are usually involved in Unifocal and multifocal unisystem LCH? 3

Skull
Ribs
Femur

152

Unifocal and multifocal unisystem LCH age?
Primary complication

Prognosis?

Young children

Diabetes insipidus

Spontaneous regression or chemo

153

Unifocal and multifocal unisystem LCH has unifocal lesions in what ages?

Older children or adults

154

Pulmonary LCH involves what patient group mainly?

Adult smokers

155

Pulmonary LCH can be defined as what better?

Reactive hyperplasia

156

Four splenic functions that impact disease states?

Phagocytosis of blood cells and particulate matter
Antibody production
Hematopoiesis
Sequestration of formed blood elements

157

Splenic insufficiency/Asplenia is due to what? 2

Splenectomy
Autoinfarction

158

Splenectomy is due to what? (2)

1. Traumatic injury that ruptures spleen
2. Hemolytic anemias

159

Autoinfarction can be due to what?

Sickle cell disease

160

Splenic insufficiency/Asplenia results in what?

What is this due to?

Doctor's reaction?

Increased susceptibility to sepsis by encapsulated bacteria

Loss of filtering and Ab production

Vaccinate these people appropriately

161

What is hypersplenism characterized by?

1. Splenomegaly
2. Anemia, leukopenia, thrombocytopenia
3. Hyperplasia of marrow precursors of deficient type

162

Correction of hypersplenism blood cytopenias is done by what?

Splenectomy

163

Massive splenomegaly is a weight of what?
Main cause?

Weight > 1000 grams

Myeloproliferative disorders

164

Moderate splenomegaly is what weight?

500-1000 grams

165

Mild splenomegaly is what weight?

< 500 grams

166

Nonspecific acute splenitis is what?

Nonspecific reaction to any blood-borne infection

167

What happens within the spleen in Nonspecific acute splenitis? 2

Congestion of red pulp with neutrophils
Plasma cells throughout spleen

168

Congestive splenomegaly definition?

What type of disorders cause this?

3 examples?

Enlargement due to chronic venous congestion

Disorders leading to splenic or portal vein hypertension

1. Central venous congestion
2. Cirrhosis of liver
3. Portal vein thrombosis

169

What is Congestive splenomegaly usually associated with?

Hypersplenism

170

Primary splenic neoplasms are how common?
Exception?
Most common type?

Very rare

Tumors in lymphohematopoietic system

Benign tumors

171

What is more common in congenital anomalies: hypoplasia or complete absence?

Hypoplasia

172

What is a common finding in congenital anomalies of spleen?

Accessory spleen (spleniculi)

173

When are accessory spleens really important? 2

Setting of splenectomy in treatment of
1. Hemolytic anemias
2. ITP

174

Splenic rupture is precipitated by what?

1. Crushing injury
2. Severe blow

175

When does spontaneous splenic rupture occur?

Minor physical insult to a spleen that is fragile by underlying condition like mono, malaria, lymph cancers

176

Are chronically enlarged spleens likely to rupture?

No. Fibrosis makes them tough

177

Thymus plays a big role in what? (2)

1. T-cell differentiation
2. CMI

178

3 frequent disorders of thymus?

1. Developmental disorder
2. Thymic hyperplasia
3. Thymoma

179

Di-Geroge syndrome definition:
Mutation:

Thymic hypoplasia or apalasia with parathyroid developmental failures
22q11.2 deletion

180

Symptoms of DiGeorge Syndrome (CATCH-22) 5

Cardiac abnormality
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia/Hypoparathyroidism

181

Why are thymic cysts important?

Thymic neoplasms are often associated with cysts

182

Does a normal thymus have lympoid follicles?

No

183

B-cell germinal centers/follicles in medulla of thymus suggest what?

Thymic Follicular Hyperplasia

184

What disease has Thymic Follicular Hyperplasia the most?
What is the treatment?

Myasthenia gravis

Thymectomy

185

Thymoma is what?

Thymic tumor in which neoplastic element is epithelial

186

3 types of thymoma?
Most common
Most malignant

1. Noninvasive (most common and benign)
2. Invasive
3. Thymic carcinoma (most malignant/severe)

187

Thymic carcinomas are usually what type of carcinoma?

Squamous cell

188

Thymomas are seen with what disease especially?

Myasthenia gravis