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WBC Path Flashcards

1
Q

bone marrow histology

A

sinusoids lined by endothelial cells with incomplete basement membrane and adventitial cells
enter blood via transcellular migration through endo
megs-adjacent to sinusoids
erythroid surround macrophages
grans hug bony trabeculae and mature centrally

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2
Q

immature phenotyp

A

CD34

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3
Q

myeloid

A

CD13, CD33, MPO (neutrophils), CD14 ,NSE (monocytes)

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4
Q

B cell

A

CD19, CD20, kappa and lambda chain

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5
Q

T cell

A

CD1, CD3, CD4, CD7, CD8, CD5

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6
Q

causes of lymphopenia

A 
drugs-steroids, cytotoxic
systemic illness or malignancy
acute viral illness-IFN causes sequestration of T cells in LN
malnutrition
immunodef
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7
Q

neutropenia causes

A

suppression-aplastic, BM infiltrative process, infection, LGL, Kostmann syndrome (hypocellular marrow)
B12/folate deficiency, copper def, MDS, SLE, drugs, splenomegaly, overwhelming infections (hypercellular marrow)

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8
Q

consequences of neutropenia

A

mucosal ulcers-oropharynx
invasive infections of bladder and kidney and lungs
treat with GCSF

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9
Q

causes of lymphocytosis

A

transient stress-MI, seizure, trauma
drugs
viral illness-EBV, CMV, pertussis (due to toxin-unique and cool)

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10
Q

neutrophilia

A

cytokines, growth factors, and adhesion molecules

50% marginated, 50% circulating (of the 25% in blood)

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11
Q

causes of reactive neutrophilia

A

minutes-epinephrine, exercise, acute stress
hours-steroids, infection, inflammation
days-infection, GCSF tumors

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12
Q

toxic changes to neutrophils

A

granules with MPO
cytoplasmic granules
left shift
Dohle bodies

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13
Q

reactive causes of eosinophilia

A

allergic response
medication/drug hypersensitivity
connective tissue disease
parasitic infection

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14
Q

neoplastic causes of eosinophilia

A

T cell LPD
Hodgkin lymphoma
Pre-B ALL (5;14)

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15
Q

causes of monocytosis

A

infections-TB, rickettsia, malaria
inflammatory-SLE, UC
myeloid neoplasms

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16
Q

lymphadenopathy

A

lymph node enlargement

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17
Q

lymphadenitis

A

lymph node inflammation due to benign reactive process

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18
Q

causes of lymphadenopathy

A 
infections
autoimmune-RA, SLE
drugs, silicone
malignant-mets, lymphoma
sarcoid
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19
Q

follicular hyperplasia

A

B cells

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20
Q

paracortical hyperplasia

A

cellular immune response

T cell expansion

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21
Q

chromosomal abnormalities in lymphoid precursors

A

inappropriate joining of VDJ recombinase cuts

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22
Q

chromosomal abnormalities in lymphoid mature

A 
germinal B cell mutation
class switch and somatic hypermutation
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23
Q

t(14;18)

A

follicular lymphoma

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24
Q

t(8;14)

A

Burkitt lymphoma

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25
Q

t(11;14)

A

mantle cell lymphoma

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26
Q

t(15;17)

A

acute promyelocytic leukemia

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27
Q

t(9;22)

A

chronic myelogenous leukemia

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28
Q

genetic instability increased risk for leukemia

A

Fanconi anemia
Bloom syndrome
Ataxia-Telangiectasia
Down syndrome and neurofibromatosis I

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29
Q

HTLV-1

A

adult T cell leukemia/lymphoma

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30
Q

HHV8

A

pleural effusion lymphoma

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31
Q

EBV

A

Burkitt lymphoma
Hodgkin lymphoma
immunodeficiency associated B cell lymphomas

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32
Q

HIV

A

increased risk of B cell lymphomas

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33
Q

H pylori

A

gastric lymphomas

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34
Q

lymphoma

A

mostly solid organ/tissue involvement

2/3 present with non-tender adenopathy

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35
Q

leukemia

A

mostly blood and/or bone marrow involvement

present with BM failure

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36
Q

plasma cell neoplasms

A

commonly arise in bone marrow

result in bony destruction

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37
Q

B type symptoms

A

fever, weight loss, night sweats

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38
Q

ALL

A

most common in children
Caucasian>black (hispanic highest incidence)
boys>girls
children>adults

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39
Q

Pre B ALL

A

highest at 4
10,19,22
34 Tdt

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40
Q

Pre T ALL

A

highest at adolescence
mediastinal mass
1,2,3,5,7
34 Tdt

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41
Q

clinical features of ALL

A 
marrow failure
sudden onset
bone pain
generalized adenopathy, hepatosplenomegaly
CNS sx
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42
Q

morphology of ALL

A

can look similar to AML
irregular contours, hand mirror
no MPO (would be present in AML)

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43
Q

B ALL cytogenetics

A

t(12;21) ETV6 and RUNX1

t(9;22) BCR ABL

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44
Q

T ALL cytogenetics

A

NOTCH

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45
Q

ALL prognosis

A

aggressive chemo and CNS prophylaxis
children better prognosis
favorable-2 to 10, low WBC, early B, trisomy 4,7,10

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46
Q

MRD

A

minimal residual disease

molecular detection after therapy is associated with worse outcome

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47
Q

CLL/SLL

A

most common leukemia of adults in the Western world

leukocytosis and mature lymphocytosis

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48
Q

clinical features CLL/SLL

A

> 50
most are asx
adenopathy, hepatosplenomegaly
infections-hypogammaglobulinemia

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49
Q

CLL morphology

A

small mature lymphs with hyperclumped nuclear chromatin and smudge cells

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50
Q

SLL morphology

A

effaced, mimic germinal centers

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51
Q

immunotype CLL/SLL

A

CD19/5/23

dim 20 and light chain restricted

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52
Q

CLL/SLL cytogenetics

A

del13q, tri12, del11q, del17p

somatic hypermutation of IGHV gene

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53
Q

CLL/SLL prognosis

A 
unmutated IGHV (CD38 and ZAP70), 17p
worse prognosis
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54
Q

Richter syndrome

A

transformation to DLBCL

rapidly enlarging lymph node and/or spleen

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55
Q

follicular lymphoma

A

NHL that mimics normal lymphoid follicles

associated with translocations involving BCL2

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56
Q

clinical features follicular lymphoma

A

painless adenopathy, generalized or localized
BM almost always involved
rarely PB involved
centroblasts-mature cells used for staging
paratrabecular aggregates in BM

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57
Q

diff follicular lymphoma from hyperplasia

A

no polarization
no tingable bodies
reverse BCL2 staining

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58
Q

immunophenotype follicular lymphoma

A

CD19/20/10

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59
Q

prognosis follicular lymphoma

A

incurable but indolent

transformation to high grade or DLBCL

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60
Q

mantle cell lymphoma

A

resembles normal mantle zone cells

tumor cells aberrantly expressed CD5 and overexpress cyclin D1

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61
Q

clinical features of mantle cell lymphoma

A

painless, generalized lymphadenopathy
BM involvement in most
lymphomatoid polyposis=GI involvement
blastoid variant is more aggressive

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62
Q

immunotype mantle cell lymphoma

A

19/20/5

bright surface light chain

63
Q

prognosis mantle cell lymphoma

A

not curable
Rituximab
indication for BM transplant

64
Q

marginal zone lymphoma

A

mostly extranodal

tumor cell resembles marginal zone cell-post germinal center memory B cell

65
Q

clinical features of marginal zone lymphoma

A 
arise in tissues from chronic inflammatory disorders
h. pylori
hashimoto
Sjogren
small bowel
lung
may regress if brought under control
66
Q

cytogenetics of marginal zone lymphoma

A

polyclonal to oligoclonal to monoclonal

acquisition of t(11;18) or t(1;14) with upregulation of BCL10 or MALT1 now independent of extrinsic stimuli

67
Q

morphology of marginal zone lymphoma

A

pleomorphic population of monoxytoid B cells and plasmacytoid cells

68
Q

DLBCL

A

high grade
most common type of NHL
most patients lack specific risk factor

69
Q

clinical features of DLBCL

A

rapidly enlarging symptomatic mass
nodal or extranodal
B symptoms
BM involvement occurs late in disease

70
Q

morphology of DLBCL

A

convoluted nuclear contours
1-3 nucleoli
mitotically active

71
Q

cytogenetics DLBCL

A

BCL6
BCL2
MYC

72
Q

immunotype DLBCL

A

CD19/20

light chain restriction

73
Q

prognosis DLBCL

A

ABC subtype is poor prognostic indicator
aggressive and fatal if untreated
RCHOP

74
Q

Burkitt lymphoma

A

high grade
African-EBV associated
Sporadic in children (20% EBV associated)
usually extranodal (abdominal mass in sporadic and mandibular in endemic)

75
Q

Tumor lysis syndrome

A

rapid cell turnover
tumor cell death releases uric acid, potassium, calcium
medical emergency requiring hydration
CNS disease occurs in most patients

76
Q

morphology of Burkitt lymphoma

A

basophilic cytoplasm with vacuoles
high mitotic
Ki-67
macrophages-starry sky

77
Q

immunotype Burkitt lymphoma

A

19/20/10
surface light chain restriction
bcl6
Ki67

78
Q

cytogenetics Burkitt lymhoma

A

t(8;14)
t(2;8)
t(8;22)

79
Q

plasma cell neoplasms

A

clonal plasma cell proliferation

M protein, Bence Jones protein

80
Q

Bence Jones protein

A

monoclonal free light chain in urine

81
Q

M protein

A

monoclonal protein secreted by plasma cell and identified in blood

82
Q

multiple myeloma

A

clonal plasma cells secrete M protein into blood or urine and cause end organ damage

83
Q

pathogenesis multiple myeloma

A

translocations involving IgH and cyclins
tumors produce IL6
activate osteoclasts/inhibit osteoblasts
hypercalcemia
IgG>A>M
inadequate normal immunoglobulin production

84
Q

clinical presentation of multiple myeloma

A 
weakenss-anemia
infections-decreased normal Ig
polyuria-hypercalcemia
bone pain
renal insufficiency-Bence Jones
amyloidosis-light chain deposition in organs
85
Q

roleaux

A

multiple myeloma blood smear

incrased protein causes them to clump like a stack of coins

86
Q

smoldering myeloma

A

> 10% clonal bone marrow plasma cells
absence of end organ damage
can progress to myeloma

87
Q

prognosis of multiple myeloma

A

death from infections and renal failure

nothing is curative

88
Q

MGUS

A

monoclonal gammopathy

periodic assessment of BJ protein and M protein to check for progression to MM

89
Q

plasmacytoma

A

solitary bone or soft tissue clonal plasma cell masses with no evidence of marrow or organ disease
can progress to myeloma
local field radiation therapy

90
Q

lymphoplasmacytic lymphoma (LPL)

A

monoclonal IgM causing hyperviscosity syndrome called Waldenstrom macroglobinemia
no light chain deposition and no bony lesions
resembles SLL

91
Q

Waldenstrom macroglobinemia

A

IgM increase viscosity
visual sx, neurologic sx, bleeding, cryoglobulinemia
plasmapheresis to alleviate sx

92
Q

mutation for LPL

93
Q

Hariy Cell leukemia

A

older male with splenomegaly and pancytopenia

BRAF mutation

94
Q

clinical featues of HCL

A

symptoms from cytopenias and splenomegaly
spleen and BM involvement
monocytopenia

95
Q

dry tap in HCL

A

due to increased reticulin fibrosis

96
Q

immunotype HCL

A

19/20/light chain restricted

11/25/103

97
Q

prognosis HCL

A

sensitive to purine analogs (cladribine)

BRAF inhibitors

98
Q

mature T cell neoplasms

A

aberrant T cell phenotype
PCR required to ID
rearrangement of TCR

99
Q

peripheral T cell lymphoma not otherwise specified

A

eosinophilia
pruritis, fever, weight loss
woser than B cell

100
Q

anaplastic large cell lymphoma

A

translocation involving ALK
found in kids
morphology-horseshoe or wreath shaped nuclei

101
Q

adult t cell leukemia/lymphoma

A

retrovirus HTLV1
CD4 T cells infected
leukemic-rapidly progressive
skin localized is less aggressive

102
Q

mycosis fungoides/sezary syndrome

A

CD4 helper T cells that home to skin
MF as patch, plaque, tumor
SS-exfoliative erythroderma plus leukemia

103
Q

appearance of MF/SS

A

cerebriform nuclear contours

104
Q

prognosis of MF/SS

A

indolent if <10% skin lifespan unaffected

mortality from immunodef

105
Q

large granular lymphocytic leukemia

A

STAT3 mutations
minimal BM infiltration but neutropenia and anemia
T/NK
associated with Felty syndrome

106
Q

Felty syndrome

A

rheumatoid arthritis-autoimmunity provoked by neoplastic cells
neutropenia
splenomegaly-infiltrates in the spleen

107
Q

Hodgkin lymphoma

A 
classical (Reed Sternberg)
nodular sclerosing-most common
mixed cellularity
lymphocyte rich
lymphocyte depleted
nodular lymphocyte predominance-LP cell (popcorn cell)
108
Q

Hodgkin lymphoma vs NHL

A 
arises in single node
spreads in contiguous fashion
neoplastic cell is Reed Sternberg cell-minority of population, reactive cells recruited by cytokines 
bimodal-young adults and peak at 45
usually curable with radiation and chemo
109
Q

Reed Sternberg cell

A

derived from germinal center or post germinal center B cells

RS in individual have identical rearranged Ig genes-somatic hypermutation

110
Q

classic RS immunotype

111
Q

NLPHL RS immunotype

112
Q

presentation of Hodgkin lymphoma

A

painless localized or generalized adenopathy
mediastinal enlargment
long term survivors have increased risk of secondary malignancies

113
Q

NSHL

A

70% of cases
cervical, supraclavicular and mediastinal nodes
lacunar cell and bands of polarizing fibrosis

114
Q

MCHL

A

mixed cellularity associated with EBV
B signs
advanced stage

115
Q

myeloproliferative neoplasms

A

effective hematopoiesis just too much of it
no dysplasia
multipotent can give rise to all myeloid (CML it is pluripotent so it can give rise to myeloid and lymphoid lines)

116
Q

MPN

A 
BCR ABL 
JAK2
MPL
CALR
PDGFR alpha
117
Q

CML

A

pluripotent stem cell abnormality

t(9;22) BCR ABL for Philadelphia chromosome

118
Q

CML morphology

A

leukocytosis with left shift
eosinophilia and basophila
packed BM with sea blue histiocytes
splenomegaly due to EMH

119
Q

clinical features of CML

A

middle age
EMH-LUQ pain
slow progression (chronic to accelerated blast)

120
Q

CML treatment

A

Imantinib

resistance can occur in subclones-does not eliminate the clone

121
Q

PV

A

must rule out secondary polycythemia
decreased EPO
JAK2 mutation

122
Q

causes of secondary polycythemia

A 
increased EPO
high altitude
chronic hypoxic disorders
hemoglobinopathies
renal transplant
neoplasm-uterine, renal, cerebellar, ovarian, hepatoma, pheo
123
Q

PV clinical features

A 
late middle age
sx from increased RBC mass
hyperuricemia due to high cell turnover
bleeding and thrombosis-abnormal places
acquired von Willebrand
minimal reticulin fibrosis
124
Q

ET

A

platelet count with abnormal large platelets
sustained thrombocytosis in blood-increased large mature megs
JAK2

125
Q

diagnosis of ET

A

exclusion

must rule out reactive, IDA, inflammation, asplenism

126
Q

clinical ET

A

thrombosis

bleeding-acquired von Willebrand syndrome

127
Q

treatment of ET

A

hydroxyurea (also used to treat sickle)

128
Q

PM

A

neoplastic megs release PDGF and TGF beta which are fibroblast mitogen
increased reticulin and collagen fibrosis
JAK2

129
Q

phases of PM

A

pre fibrotic-thrombocytosis could be ET or reactive

fibrotic-anemia, early satiety

130
Q

MDS

A

depends on blast count

clonal stem cell abnormality resulting in ineffective hematopoiesis with dysplasia

131
Q

MDS morphology

A

PB-cytopenic with anemia, dysplasic neutrophils, platelets
BM-hypercellular, blasts<20%
increase in iron storage

132
Q

MDS genetics

133
Q

MDS treatment

A

supportive care with transfusions, antibiotics
Vidaza
Allo-stem cell transplant

134
Q

AML-myeloblast

A

Auer rods
34/13/33
MPO positive

135
Q

AML-monoblast

A

11/14/33/64

NSE positive

136
Q

AML pathophysiology

A

acquired genetic alteration-RUNX1, RARA
mutation in signal transduction-JAK2
>20% blasts
hypercellular leads to pancytopenia

137
Q

AML presentation

A

due to bone marrow failure
fatigue, pallor-anemia
bruising and petechiae-thrombocytopenia
infections-neutropenia

138
Q

granulocytic sarcoma

A

tissue mass of blasts in absence of PB or BM involvement (will progress to AML if left untreated)

139
Q

AML with recurrent cytogenetic abnormalities

A

Acute promyelocytic leukemia
associated with DIC
RARA (15;17)

140
Q

AML with gene mutations

141
Q

AML with myelodysplasia related change

A

poor prognosis-behaving aggressively

142
Q

Splenomegaly

A

HCL, primary fibrotic hyperplasia
LUQ dragging sensation
discomfort after eating

143
Q

nonspecific acute splenitis

A

blood borne infection
softness
congestion of red pulp

144
Q

congestive splenomegaly-intrahepatic

A

RHF

hepatic cirrhosis

145
Q

congestive splenomegaly-extrahepatic

A

spontaneous portal vein thrombosis

splenic vein thrombosis

146
Q

pathologic findings of splenomegaly

A

firmness

sugar coating

147
Q

splenic infarcts

A

pale, wedge shaped and subcapsular in location

associated with infective endocarditis

148
Q

accessory spleen

A

in gastrosplenic ligament, tail of pancreas, omentum, large/small bowel mesenteries
only important in hereditary spherocytosis-becomes dominant spleen if not removed

149
Q

thymic hyperplasia

A

secondary follicles

associated with myasthenia gravis, graves, SLE, RA

150
Q

thymoma

A

tumor of epithelial cells with background of immature T cells
anterior superior mediastinum of adults

151
Q

benign thymoma

A

encapsulated

medullary or mixed medullary and cortical epithelial cells

152
Q

malignant thymomas

A

cytologically benign but invasive-cortical epithelial cells

cytologically malignant-squamous cell carcinoma, lymphoepithelioma EBV

153
Q

langerhans cell histiocytosis

A

tumor from dendritic cells
express HLA-DR, S-100, CD1
Birbeck granules
tennis racket on EM

DT1 (4 decks)

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