CH6 - White Blood Cell Disorders Flashcards Preview

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Flashcards in CH6 - White Blood Cell Disorders Deck (283):
1

What does hematopoetic CD34+ stem cells produce?

Myeloid stem cells and lymphoid stem cells

2

What does myeloid stem cells produce?

Erythroblast, Myeloblast, Monoblast, Megakaryoblast

3

What does erythroblast produce?

RBCs

4

What does myeloblast produce?

Neutrophils, basophils, Eosinophils

5

What does monoblast produce?

Monocytes

6

What does megakaryoblast produce?

megakaryocytes

7

What does lymphoid stem cells produce?

B lymphoblast and T Lymphoblast

8

What does B lymphoblast produce?

Naïve Bcells

9

What does Naïve B cells produce?

Plasma cells

10

What does T lymphoblast produce?

Naïve Tcells

11

What does Naïve T cells produce?

CD8+ and CD4+ T cells

12

How does hematopoiesis occur?

via a stepwise maturation of CD34+ hematopoietic stem cells

13

What happens to hematopoetic stem cells?

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

14

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

it is approximately 5-10 K/pL

15

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

(< 5 K) is called leukopenia.

16

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

(> 10 K) is called leukocytosis.

17

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

a decrease or increase in one particular cell lineage.

18

What is neutropenia?

refers to a decreased number of circulating neutrophils

19

What are some of the causes of neutropenia?

1) Drug toxicity 2) severe infection

20

How can drug toxicity lead to neutropenia?

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

21

How does severe infection lead to neutropenia?

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

22

What is GM-CSF or G-CSF?

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

23

What is lymphopenia?

it refers to a decreased number of circulating lymphocytes

24

What are the some of the causes of lymphopenia?

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

25

What are some examples of immunodeficiency that lead to lymphopenia?

e.g., DiGeorge syndrome or HIV

26

How does a High Cortisol state lead to lymphopenia?

exogenous corticosteroids or Cushing syndrome, induces apoptosis of lymphocytes

27

What is an example of autoimmune destruction leading to lymphopenia?

e.g., systemic lupus erythematosus

28

How can whole body radiation lead to lymphopenia?

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

29

What are the different types of leukocytosis?

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

30

What does neutrophilic leukocytosis refer to?

increased circulating neutrophils

31

What are the causes of neutrophilic leukocytosis?

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

32

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

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

33

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

by decreased Fc receptors

34

What is the marker for the decreased Fc receptor?

CD16

35

Why are Fc receptors important?

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

36

How does high cortisol state lead to neutrophilic leukocytosis?

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

37

What does monocytosis refer to?

increased circulating monocytes

38

What are the causes of monocytosis?

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

39

What does eosinophilia refer to?

increased circulating eosinophils

40

What are the causes of eosinophilia?

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

41

What is eosinophilia driven by?

increased eosinophil chemotactic factor

42

What does basophilia refer to?

increased circulating basophils

43

What is basophilia classically seen in?

chronic myeloid leukemia

44

What does lymphocytic leukocytosis refer to?

increased circulating lymphocytes

45

What are the causes of lymphocytic leukocytosis?

1) viral infection 2) Bordetella pertussis infection

46

How does viral infections lead to lymphocytic leukocytosis?

T lymphocytes undergo hyperplasia in response to virally infected cells

47

How does Bordetella pertussis infection lead to lymphocytic leukocytosis?

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

48

What is infectious mononucleosis?

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

49

How is EBV transmitted?

by saliva (kissing disease); classically affects teenagers

50

What does EBV primarily infect?

1. Oropharynx, resulting in pharyngitis 2. Liver, resulting in hepatitis with hepatomegaly and elevated liver enzymes 3. B cells

51

CD8+ T-cell response leads to what?

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

52

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

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

53

How does CD8+ T cell response lead to splenomegaly?

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

54

What is used for screening of IM?

The monospot test

55

What does the monospot test do?

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

56

When would the monospot test turn positive?

Usually turns positive within 1 week after infection

57

What would a negative monospot test suggest?

CMV as a possible cause of IM

58

How is a definitive diagnosis for IM made?

by serologic testing for the EBV viral capsid antigen.

59

What are the complications of EBV?

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

60

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

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

61

When might a rash develop as a complication of EBV?

if exposed to ampicillin

62

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

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

63

What is acute leukemia?

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

64

What is the acute presentation for acute leukemia?

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

65

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

Increased blasts crowd-out normal hematopoiesis,

66

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

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

67

Describe blasts.

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

68

What is acute leukemia subdivided into?

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

69

The subdivision of acute leukemia is based on what?

the phenotype of the blasts.

70

What is acute lymphoblastic leukemia?

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

71

Why is TdT useful in characterizing lymphoblasts?

It is absent in myeloid blasts and mature lymphocytes.

72

Acute lymphoblastic leukemia most commonly arises in whom?

children

73

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

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

74

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

B-ALL and T-ALL based on surface markers

75

What is the most common type of ALL?

B-ALL

76

What is B-ALL usually characterized by?

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

77

What is the treatment for B-ALL?

Excellent response to chemotherapy; requires prophylaxis to scrotum and CSf

78

What is the prognosis B-ALL based on?

It is based on cytogenetic abnormalities,

79

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

t(12;21)

80

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

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

81

What is T-ALL characterized by?

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

82

How does T-ALL usually present?

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

83

What is acute myeloid leukemia?

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

84

How are myeloblasts usually characterized?

by positive cytoplasmic staining for myeloperoxidase (MPO)

85

What may be seen in the characterization of myeloblasts?

Crystal aggregates of MPO may be seen as Auer rods

86

In whom does acute myeloid leukemia most commonly arise?

older adults (average age is 50-60 years)

87

What is the subclassification of AML based on?

cytogenetic abnormalities, lineage of myeloblasts, and surface markers.

88

What are the high-yield subtypes?

Acute promyelocytic leukemia, Acute monocytic leukemia and acute megakaryoblastic leukemia

89

What is acute promyelocytic leukemia characterized by?

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

90

What is the effect of RAR disruption?

It blocks maturation and promyelocytes (blasts) accumulate

91

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

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

92

What is the treatment for acute promyelocytic leukemia?

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

93

How does ATRA work?

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

94

What is acute monocytic leukemia?

Proliferation of monoblasts; usually lack MPO

95

In acute monocytic leukemia what do blasts characteristically do?

infiltrate gums

96

What is acute megakaryoblastic leukemia?

Proliferation of megakaryoblasts; lack MPO

97

What is acute monocytic leukemia associated with?

Down syndrome (usually arises before the age of 5)

98

What is myelodysplastic syndrome?

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

99

What do myelodysplastic syndromes usually present with?

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

100

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

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

101

What is chronic leukemia?

Neoplastic proliferation of mature circulating lymphocytes

102

What is chronic leukemia characterized by?

a high WBC count

103

Describe the onset of chronic leukemia?

Usually insidious in onset and seen in older adults

104

What is chronic lymphocytic leukemia?

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

105

What is the most common leukemia overall?

Chronic lymphocytic leukemia (CLL)

106

In CLL what is seen on the blood smear?

Increased lymphocytes and smudge cells are seen on blood smear

107

small lymphocytic lymphoma

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

108

What are the complications of CLL?

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

109

What is the most common of death in CLL?

infection

110

What is Richter transformation?

transformation to diffuse large B-cell lymphoma

111

What is Richter transformation marked clinically by?

an enlarging lymph node or spleen

112

What is Hairy cell leukemia?

Neoplastic proliferation of mature B cells

113

What characterizes hairy cell leukemia?

hairy cytoplasmic processes

114

What are hairy cell leukemia cells positive for?

tartrate-resistant acid phosphatase (TRAP).

115

What are the clinical features for hairy cell leukemia?

Splenomegaly, dry tap on bone marrow aspiration

116

Why is there splenomegaly in hairy cell leukemia?

Due to accumulation of hairy cells in red pulp

117

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

due to marrow fibrosis

118

How is lymphadenopathy related to hair cell leukemia?

Lymphadenopathy is usually absent

119

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

2-CDA (cladribine)

120

How does hair cell leukemia respond to cladribine?

excellent response

121

How does cladribine work?

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

122

What is adult T cell leukemia?

Neoplastic proliferation of mature CD4+ T cells (ATLL)

123

What is adult T cell leukemia associated with?

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

124

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

Japan and the Caribbean

125

What are the clinical features for ATLL?

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

126

What is mycosis fungoides?

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

127

What are Patitrier microabscesses?

Aggregates of neoplastic cells in the epidermis

128

Sezary syndrome

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

129

What are Sezary cells?

Characteristic lymphocytes with cerebri form nuclei

130

What would you see on blood smear in mycosis fungoides?

Sezary cells

131

What are myeloproliferative disorders?

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

132

What does myeloproliferative disorders result in?

high WBC count with hypercellular bone marrow

133

How are myeloproliferative disorders characterized?

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

134

What are the complications for myeloproliferative disorders?

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

135

What is chronic myeloid leukemia?

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

136

In chronic myeloid leukemia what are characteristically increased?

basophils

137

What is chronic myeloid leukemia driven by?

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

138

What is the first line treatment for chronic myeloid leukemia?

imatinib,

139

What does imatinib do?

It blocks tyrosine kinase activity

140

How is splenomegaly related to chronic myeloid leukemia?

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

141

In chronic myeloid leukemia what usually follows after splenomegaly?

transformation to acute leukemia

142

What can chronic myeloid leukemia transform to?

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

143

What is a leukemoid reaction?

Reactive neutrophilic leukocytosis

144

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

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

145

What is a LAP stain?

leukocyte alkaline phosphatase (LAP) stain

146

How is a LAP stain related to a leukemoid reaction?

granulocytes in a leukemoid reaction are LAP positive

147

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

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

148

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

It is present in CML and absent in leukemoid reaction

149

What is polycythemia vera?

Neoplastic proliferation of mature myeloid cells, especially RBCs

150

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

Granulocytes and platelets are also increased

151

What mutation is associated with polycythemia vera?

JAK2 kinase mutation

152

What are the clinical symptoms for polycythemia vera due to?

they are mostly due to hyperviscosity of blood

153

What are the clinical symptoms for polycythemia vera?

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

What is plethora in relation to PV?

One of the clinical symptoms; flushed face due to congestion

155

Why is there itching in PV?

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

156

What is the treatment for PV?

phlebotomy;

157

What is the second-line therapy for PV?

hydroxyurea.

158

What happens to a patient with PV who goes intreated?

Without treatment, death usually occurs within one year.

159

How can PV be distinguished from reactive polycythemia?

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

What are the EPO and SaO2 levels in PV?

EPO is decreased and SaO2 is normal

161

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

EPO is increased and SaO2 is low

162

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

EPO is high, SaO2 is normal

163

What is essential thrombocythemia?

Neoplastic proliferation of mature myeloid cells, especially platelets

164

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

RBCs and granulocytes are also increased.

165

What is mutation is ET associated with?

JAK2 kinase mutation

166

What do the symptoms of ET result from?

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

167

What do the symptoms of ET rarely progresses to?

marrow fibrosis or acute leukemia

168

In ET what is there no significant risk for?

hyperuricemia or gout

169

What is myelofibrosis?

It is neoplastic proliferation of mature myeloid cells, especially megakaryocytes

170

What mutation is associated with myelofibrosis?

JAK2 kinase mutation in 50% of cases

171

In myelofibrosis, what causes marrow fibrosis?

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

172

What are the clinical features for myelofibrosis?

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

173

In myelofibrosis what is splenomegaly due to?

extramedullary hematopoiesis

174

In myelofibrosis what is the leukoerythroblastic smear?

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

175

What is lymphadenopathy (LAD)?

it refers to enlarged lymph nodes

176

Painful LAD is usually seen in what?

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

177

Painless LAD can be seen with what?

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

178

In inflammation, lymph node enlargement is due to what?

hyperplasia of particular regions of the lymph node

179

What is follicular hyperplasia seen with?

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

180

What is paracortex hyperplasia seen with?

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

181

What is involved with hyperplasia of sinus histiocytes?

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

182

What is lymphoma?

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

183

What is lymphoma divided into?

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

184

NHL further classified based on what?

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

What are some examples of small B cells?

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

186

What are some examples of intermediate-sized B cells

Burkitt lymphoma

187

What are some examples of large B cells

diffuse large B-cell lymphoma

188

What is the overall frequency for NHL?

60%

189

What is the overall frequency for HL?

40%

190

What are the malignant cells of NHL?

Lymphoid cells

191

What are the malignant cells of HL?

Reed-Sternberg cells

192

What is the composition of mass for NHL?

lymphoid cells

193

What is the composition of mass of HL?

Predominantly reactive cells (inflammatory cells and fibrosis)

194

How does NHL present clinically?

Painless lymphadenopathy, usually arises in late adulthood

195

How does HL present clinically?

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

196

What is the spread of NHL?

Diffuse: often extranodal

197

What is the spread of HL?

Contiguous; rarely extra nodal

198

Do you use staging in NHL?

Limited importance

199

Do you use staging in HL?

Guides therapy; radiation is the mainstay of treatment.

200

Is there a Leukemic phase in lymphoma?

Occurs in NHL but not in HL

201

What is follicular lymphoma?

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

202

How does follicular lymphoma present clinically?

in late adulthood with painless lymph adenopathy

203

What is follicular lymphoma driven by?

t(14;18)

204

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

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

205

What is the treatment for follicular lymphoma?

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

206

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

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

207

How is follicular lymphoma distinguished from reactive follicular hyperplasia?

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

What is mantle cell lymphoma?

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

209

How does mantle cell lymphoma present clinically?

presents in late adulthood with painless lymph adenopathy

210

What is mantle cell lymphoma driven by?

t(ll;14)

211

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

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

What is marginal zone lymphoma?

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

213

What is marginal zone lymphoma associated with?

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

214

What is the marginal zone formed by?

post-germinal center B cells.

215

What is MALToma?

it is marginal zone lymphoma in mucosal sites.

216

How might Gastric MALToma regress

with treatment of H Pylori,

217

What is burkitt lymphoma?

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

218

What is butkitt lymphoma associated with?

EBV

219

How does burkitt lymphoma classically present?

as an extranodal mass in a child or young adult

220

What is specific about the african form of burkitts lymphoma?

usually involves the jaw

221

What does the sporadic form of Burkitts lymphoma usually involve?

the abdomen

222

What is Burkitt lymphoma driven by?

Driven by translocations of c-myc (chromosome 8)

223

What is the most common translocation for Burkitts lymphoma?

t(8;14) is most common,

224

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

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

225

What does overexpression of c-myc oncogene do?

promotes cell growth

226

How is Burkitts lymphoma characterized?

by high mitotic index and 'starry-sky' appearance on microscopy

227

What is diffuse large B-cell lymphoma?

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

228

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

Diffuse large B-cell lymphoma

229

Describe diffuse large B-Cell lymphoma clinically?

Clinically aggressive (high-grade)

230

How does diffuse large B-cell lymphoma arise?

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

231

How does diffuse large B-cell lymphoma present?

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

232

What is Hodgkins Lymphoma?

Neoplastic proliferation of Reed-Slernberg (RS) cells,

233

What are Reed-Slernberg cells?

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

234

Hodgkins lymphoma is classically positive for what?

CD15 and CD30

235

What do RS cells secrete?

cytokines.

236

What are the symptoms for HL

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

237

In HL what do the RS cells attract?

reactive lymphocytes, plasma cells, macrophages, and eosinophils

238

What may the RS cells in HL lead to?

fibrosis

239

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

Reactive inflammatory cells

240

What are the subtypes of reactive inflammatory cells in HL?

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

241

What is the most common subtype of HL?

Nodular sclerosis (70% of all cases),

242

What is the classic presentation for nodular sclerosis?

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

243

Dsecribe the lymph node in nodular sclerosis?

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

244

What are lacunar cells?

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

245

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

Lymphocyte-rich

246

In HL mixed cellularity is often associated with what?

abundant eosinophils (RS cells produce IL-5).

247

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

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

248

What are the plasma cell disorders?

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

249

What is multiple myeloma?

Malignant proliferation of plasma cells in the bone marrow

250

Whis the most common primary malignancy of bone?

metastatic cancer,

251

What is the most common malignant lesion of bone overall?

Multiple myeloma

252

In multiple myeloma what is usually present?

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

253

What are the clinical features for multiple myeloma?

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

Why is there bone pain with hypercalcemia in multiple myeloma?

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

255

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

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

256

Why is there elevated serum protein in multiple myeloma?

Neoplastic plasma cells produce immunoglobulin;

257

In multiple myeloma, what is seen on electrophoresis?

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

258

In multiple myeloma why is there increased risk of infection?

Monoclonal antibody lacks antigenic diversity

259

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

infection

260

Why is there rouleaux formation of RBCs on blood smear?

increased serum protein decreases charge between RBCs

261

Why is there primary AL amyloidosis in multiple myeloma?

Free light chains circulate in serum and deposit in tissues.

262

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

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

What is monoclonalgammopathy of undetermined significance?

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

MGUS is common in what group of people?

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

265

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

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

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What is Waldenstrom macroglobulinemia?

B-cell lymphoma with monoclonal IgM production

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What are the clinical features for waldenstrom macroglobulinemia?

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

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Why is there bleeding in waldenstrom macroglobulinemia?

Viscous serum results in defective platelet aggregation

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What are the complications for waldenstrom macroglobulinemia treated with?

plasmapheresis, which removes IgM from the serum

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What are langerhans cells?

specialized dendritic cells found predominantly in the skin.

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What are langerhans cells derived from?

bone marrow monocytes

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What do langerhans cells present?

Present antigen to naive T cells

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What is langerhans cell histiocytosis?

it is a neoplastic proliferation of Langerhans cells

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What is seen on electron microscopy in langerhan cell histiocytosis?

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

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What is langerhan cell histiocytosis immunochemistry?

cells are CDla+ and S100+

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What is Letterer-Siwe disease?

Malignant proliferation of Langerhans cells

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What is the classic presentation of Letterer-Siwe?

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

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Can Letterer-Siwe be fatal?

Multiple organs may be involved; rapidly fatal

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What is eosinophilic granuloma?

Benign proliferation of Langerhans cells in bone

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What is the classic presentation for eosinophilic granuloma?

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

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What does biopsy of eosinophilic granuloma show?

Langerhans cells with mixed inflammatory cells, including numerous eosinophils

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What is Hand-Schuller-Christian disease?

Malignant proliferation of Langerhans cells

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

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