Chapter 6 White Blood Cell Disorders Flashcards
(121 cards)
1
Q
What is the CD marker of a hematopoietic stem cell?
A
CD34
2
Q
What are two major causes of neutropenia?
A
Drug toxicity ( eg chemo with alkylating agents) - damage to stem cells results in decreased production of WBCs especially neutrophils. Severe infection (Gram neg sepsis) increased movement of neutrophils into tissues
3
Q
What treatment can be used to boost granulocyte production?
A
G-CSF or GM-CSF
4
Q
What are some major causes of lymphopenia?
A
1 Immunodeficiency (DiGeorges and HIV)
2 High Cortisol state (exogenous coricosteroids or cushing syndrome) induces apoptosis in lymphocytes
3 Autoimmune destruction ( SLE)
4 Total Body irradiation
5
Q
Name two causes of neutrophilic leukocytosis?
A
1 Bacterial infection or tissue necrosis induces release of marginal pool, and bone marrow neutrophils including immature forms (Bands)
2 High Cortisol states impair leukocytes adhesion leading to release of marginated pools.
6
Q
What cell marker will band forms be lacking in?
A
CD16 which is Fc receptors
7
Q
What are a couple causes of monocytosis?
A
chronic inflammatory states (autoimmune and infectious) and malignancy
8
Q
What are 3 causes of eosinophilia?
A
allergic reactions, parasitic infections, hodgkin lymphoma.
9
Q
What is the eosinophilic chemotactic factor?
A
IL-5
10
Q
What is a classic setting for basophilia?
A
CML
11
Q
What are two causes of lymphocytic leukocytosis?
A
Viral infections- Tcell hyperplasia
Bordetella pertussis infection
12
Q
In bordetella pertussis infection what causes lymphocytosis?
A
release of lymphocytosis-promoting factor blocks circulating lymphocytes from entering lymph node.
13
Q
What type of leukocytosis is caused by EBV?
A
Lymphocytic reactive CD8 T cells
14
Q
What does EBV primarily infect in IM? (body parts)
A
Oropharynx
liver resulting in hepatitis with hepatomegaly and elevated liver enzymes
B - Cells
15
Q
What does the CD8 Tcell response in EBV IM lead to?
A
Generalized LAD
Splenomegaly due to proliferation in PALS
High WBC with atypical lymphocytes (reactive CD8)
16
Q
What does the monospot test detect? if it is negative what does this point to?
A
Detects IgM antibodies against horse or sheep RBCs (heterophile antibodies)
negative indicates CMV as IM cause.
17
Q
What are some complications of IM?
A
risk fro splenic rupture
rash with penicillin
dormancy in B cels can lead to recurrance and B-cell lymphoma.
18
Q
What is acute leukemia a neoplastic proliferation of? What is the threshold for % of blasts
A
blasts; defined as the accumulation of >20% blasts in the bone marrow.
19
Q
What are the effects of increased blasts in acute leukemia on bone marrow production?
A
increased blasts crowd-out normal hematopoiesis resulting in pancytopenia
20
Q
What effect does acute leukemia have on the WBC and peripheral smear?
A
blasts usually enter the blood stream resulting in a high WBC with blasts on peripheral smear.
21
Q
What are some histological features of blasts (what do they look like)?
A
they are large immature cells often with punched out nucleoli
22
Q
What nuclear stain can be used to identify ALL and differentiate it from AML and CLL?
A
Tdt, a DNA polymerase that is not present in myeloid blasts or mature lymphocytes.
23
Q
What is the most common ALL demographic? What other pathology is it associated with?
A
Commonly arises in children after the age of 5; associated with DS
24
Q
What is more common B-ALL or T-ALL?
A
B-ALL
25
What is the treatment of B-ALL, does it work?
Excellent response to chemotherapy; requires prophylaxis to scrotum and CSF
26
What markers are present for good prognosis in ALL?
early precursor B-cell type, hyperdiploidy, patient between 7-10, chromosomal trisomy, and t(12;21)
27
What identifying histochemical characteristics are seen in B-ALL (markers)
TdT+, CD10, CD19, CD20
28
What are the cell markers for T-ALL?
TdT+ and markers ranging from CD2-CD8.
| NO CD10
29
What demographic does T-ALL present in?
Teenagers as a mediastinal mass (usually thymus) it is called acute lymphoblastic lymphoma due to the presence of a mass
30
What cytoplasmic staining is seen in AML?
myeloperoxidase (MPO)
31
What is myeloperoxidase function in the immune system?
MPO is in neutrophils to produce hypochlorus acid from H2O2 and Cl- during the respiratory burst.
32
What are auer rods?
crystal aggregates of MPO in AML cells
33
What demographic does AML normally arise in?
older adults (50-60 years old)
34
What translocation is seen in APL?
t(15;17) prevents maturation
35
What serious hematological complications can arise from APL?
DIC, auer rods increase risk.
36
What area of the body do blasts in Acute monocytic leukemia usually infiltrate? How do these cells differ from APL cells as far as stains go?
Gums, Lack MPO
37
What condition is acute megakaryoblastic leukemia associated with? Do these blasts contain MPO?
DS (usually presents before 5)
| No MPO
38
What underlying condition can lead to AML?
myelodysplastic syndrome especially after exposure to alkylating agents or radiotherapy.
39
Chronic Leukemia is a neoplastic proliferation of what cell? What hematological finding is it characterized by (general)?
Mature circulating lymphocytes resulting in a high WBC
40
Describe the onset and demographic in Chronic leukemia?
Insidious onset and seen in older adults
41
What neoplastic proliferation is seen in CLL? What cell markers are present?
proliferation of Naive B-Cells express CD5 and CD20
42
What abnormalities are seen on smears in CLL?
Increases lymphocytes and smudge cells
43
Involvement of the lymph nodes in CLL leads to generalized LAD and is called what?
Small lymphocytic lymphoma
44
Name 3 complications seen in CLL?
1 hypogammaglobulinemia (Cells dont differentiate into plasma cells)
2 Autoimmune hemolytic anemia
3 transformation to diffuse large B-cell lymphoma (marked by focal lymph enlargement)
45
What is the most common cause of death in CLL?
Infection (due to hypogammaglobulinemia)
46
What proliferation is seen in Hairy Cell Leukemia
proliferation of mature B-Cells characterized by hairy cytoplasmic processes
47
What are HCL cells positive for?
Tartrate-resistant acid phosphatase (TRAP)
48
What clinical features are seen in HCL?
splenomegaly due to accumulation in red pulp, dry tap aspiration due to marrow fibrosis, LAD is usually absent
49
What is the treatment fro HCL?
2-CDA (Cladribine) an adenosine deaminase inhibitor; adenosine accumulates to toxic levels
50
What neoplastic proliferation is seen in Adult T Cell leukemia/lymphoma?
Mature CD4+ Tcells
51
What demographic and virus is ATLL seen in?
HTLV-1 virus in japan and caribbean
52
What clinical features are seen in ATLL
rash (skin infiltration), generalized LAD with hepatosplenomegaly. lytic punched out bone lesions with hypercalcemia
53
What neoplastic proliferation is seen in Mycosis Fungoides?
Mature CD4+ Tcells
54
What are the clinical features of mycosis fungoides?
cells infiltrate the skin, producing localized skin rash, plaques, and nodules. Aggregates of neoplastic cells in the epidermis are called Pautrier microabscesses
55
What is Sezary Syndrome? what is seen on smears?
When mycosis fungoides spread to the blood, it is characterized by lymphocytes with cerebriform nuclei (sezary cells)
56
What neoplastic proliferation is seen in MPDs?
mature cells of myeloid lineage
57
What demographic are MPDs seen in?
Late adulthood
58
What hematological changes are seen in all MPDs?
high WBC due to increase synth of all lineages with one predominant and hypercellular marrow
59
What 2 general complications can arise from MPDs?
1 Increased risk for hyperuricemia and gout due to high turnover of cells
2 Progression to marrow fibrosis or transformation to acute leukemia.
60
What are the 4 main MPDs?
CML, PV, ET, and myelofibrosis
61
What particular proliferation is seen in CML?
granulocytes; characteristically basophils
62
What marks the accelerated phase of CML?
splenomegaly is common in general but an actively enlarging spleen indicates the accelerated phase
63
What can CML transform into? what does this say about the cell of origin?
AML or ALL meaning it must be a mutation in a pluripotent stem cell
64
How is CML distinguished from a leukemoid reaction?
Negative leukocyte alkaline phosphatase (LAP)
increased basophils
t(9;22)
65
What mutation is associated with polycythemia vera and what cell dominates proliferation?
JAK2 kinase dominated by RBCs
66
What are the clinical symptoms of PV and what are they due to?
Symptoms due to hyperviscosity
blurry vision
increased risk of venous thrombosis
flushed face due to congestion (plethora)
itching, especially after bathing due to increased mast cells
67
What is the treatment form PV?
Phlebotomy; second line is hydroxyurea
68
What mutation is seen in essential thrombocytopenia and what is the dominant cell?
JAK2 kinase and platelets
69
What are the symptoms of ET related to? Does it commonly progress to marrow fibrosis or AL, is there a significant risk for hyperuricemia?
increased risk for thrombosis and or bleeding (platelets can be under or overfunctioning)
Rarely progresses, no increased risk of gout bc no nucleus turnover
70
What mutation is Myelofibrosis associated with and what is the dominant cell?
JAK2 kinase and megakaryocyte
71
What causes marrow fibrosis in myelofibrosis?
excess production of platelet derived growth factor by megakaryocytes
72
What are the clinical features of Myelofibrosis (3)?
1 Splenomegaly due to extramedullary hematopoiesis
2 Leukoerythroblastic smear (tear drop RBCs, nucleated RBCs, and immature granulocytes)
3 increased risk of infection, thrombosis, and bleeding (spleen cannot completely compensate)
73
What are two examples of when you would see follicular hyperplasia in a lymph nodes?
rheumatoid arthritis and early stage HIV
74
What is an example of when you would see paracortex hyperplasia in lymph nodes?
Viral infections
75
What is an example of when you would see hyperplasia of sinus histiocytes in lymph nodes?
Node draining a tissue with cancer
76
What type of cells are proliferating a follicular lymphoma?
small B-cells CD20+ that form a follicle like nodule
77
What translocation is seen in follicular lymphoma?
t(14;18) (Bcl2 and IgH)
78
How is follicular lymphoma distinguished from reactive follicular hyperplasia. 4 ways
1 disruption of normal lymph node architecture
2 lack of tingible macrophages
3 overexpression of bcl2
4 monoclonality
79
What proliferation is seen in mantle cell lymphoma? what translocation?
small B-cells (CD20+) t(11;14) Cyclin D1 and IgH
80
What proliferation is seen in marginal zone lymphoma? what type of cells are these
small B-cells (CD20+) formed by POST germinal center B-cells
81
What is marginal zone lymphoma associated with?
Associated with chronic inflammatory states such as hashimotos, Sjorgen, and H pylori. MALToma is a marginal zone lymphoma of mucosal sites
82
What proliferation is seen in Burkitt cell lymphoma? what is the translocation?
intermediate size b cells (CD20+) t(8;14) cMYC
83
What demographic does burkitt lymphoma generally present in?
extranodal mass in a child or young adult
84
What two variants of burkitt lymphoma are there and what sites do they present in?
African - jaw
| sporadic involves abdomen
85
What microscopic characteristics are seen in burkitt lymphoma?
High mitotic index and 'starry skied' appearance
86
What is the proliferation seen in diffuse large B cell lymphoma? how does it usually present? how do the cells grow?
Large B-cells (CD20+)
Arises sporadically or from transformation in late adulthood as an enlarging lymph node
cells grow diffusely in sheets
87
What is the proliferation seen in Hodgkins lymphoma and what are the cell markers?
Reed-Sternberg cells which are large B-cells with multilobed nuclei and prominent nucleoli classically positive for CD15 and CD30
****NO CD20****
88
RS cells in HL secrete cytokines, what does this lead to?
Occasional 'B' symptoms (fevers chills, weight loss, and night sweats)
attract lymphocytes, plasma cells, macrophages, and eosinophils
may lead to fibrosis
89
What is the most common type of HL? What is it characterized by and how does it present?
Nodular sclerosis characterized by lymph node divided by bands of sclerosis with RS cells in lake like spaces (lacunar). Presents as an enlarging cervical or mediastinal lymph node in a young adult usually a female
90
Which type of HL has the best prognosis?
Lymphocyte rich
91
Which type of HL is associated with abundant eosinophils?
Mixed cellularity (secretion of IL 5)
92
Which type of HL is most aggressive?
Lymphocyte depleted
93
What type of proliferation is seen in multiple myeloma?
Plasma cells in bone marrow
94
Levels of what cytokine are raised in multiple myeloma? What does this do?
IL 6 which stimulates plasma cell growth and immunoglobulin production
95
Name six clinical signs of multiple myeloma?
```
1 Bone pain with hypercalcemia
2 elevated serum protein
3 increased risk of infection
4 rouleaux formation of RBCs on smear
5 Primary AL amyloidosis
6 Proteinuria
```
96
What causes bone pain and hypercalcemia in Multiple myeloma?
neoplastic plasma cells secrete RANKL which activates osteoclasts
97
What causes elevated serum protein in multiple myeloma?
plasma cells produce immunoglobulin which presents as an M Spike on SPEP most commonly due to monoclonal IgA or IgG
98
What caused increased risk of infection in multiple myeloma?
Monoclonal antibodies lack antigenic diversity
99
What causes rouleaux formation in multiple myeloma?
increased serum protein decreases charge between RBCs
100
What causes primary AL amyloidosis in multiple myeloma?
free light chains circulate in serum and deposit in tissues
101
What causes proteinuria in multiple myeloma?
free light chain is secreted in the urine as Bence Jones protein; deposition in kidney tubules leads to risk for renal failure
102
What is Waldenstrom Macroglobulinemia?
B-cell lymphoma with monoclonal IgM production
103
What are clinical signs of waldenstrom macroglobulinemia?
Generalized LAD
M spike due to IgM
Visual and neuro deficits due to serum hyperviscosity
treat with plasmapheresis
104
What are langerhans cells?
Specialized dendritic cells found predominantly in the skin
105
What are langerhans cells made from and what do they do?
They are derived from bone marrow monocytes and present antigen to T cells
106
What is characteristic of langerhans cell histiocytosis on EM and immunohistochemistry?
Characteristic Birbeck (tennis racket) granules and cells are CD1a+ and S100+
107
What is Letterer Siwe Disease?
Malignant proliferation of langerhans cells classically presents as skin rash and cystic skeletal defects in infant (<2). multiple organs may be involved and it is rapidly fatal
108
What is Eosinophillic granuloma?
Benign proliferation of langerhans cells in the bone. Classic presentation is pathologic fracture in aldolescent, skin not involved. Biopsy shows langerhans cells with mixed inflammatory cells, including numerous eosinophils
109
What is Hand-Schuller-christian disease?
Malignant proliferation of langerhans cells. Classic presentation is scalp rash, lytic skill defects, diabetes insipidus, and exopthalmos in a child (>3)
110
What are the atypical lymphocytes seen in IM? what makes them atypical?
Reactive CD8+ T cells which look like monocytes. They are atypically large and have blue cytoplasm.
111
how do myelodysplastic syndromes typically present?
cytopenias, hypercellular marroy, abnormal maturation, and increased blasts (However <20%)
112
What are some cytological markers of post-therapy myelodysplasia?
Chromosomal deletions such as 5q
113
What type of HL is EBV associated with in over 90% of cases?
Lymphocyte depleted
114
What histological properties can help differentiate myeloblasts from lymphoblast?
Azurphilic, peroxidase positive granules.
115
What chromosomal rearrangement is seen in Digeorges syndrome?
22q11.2
116
What markers indicate poor prognosis in ALL?
T cell phenotype, patient younger than 2, WBC > 100K, and t(9;22)
117
What is the characteristic gene rearrangement seen in Anaplastic large cell lymphoma (t cells)
rearrangement 2p23 that results in production of anaplastic lymphoma kinase with tyrosine kinase activity.
118
What is cat scratch disease caused by, what are the signs?
caused by rochailimaea Henselae and results in lymphadenopathy with microscopic stellate necrosis. self limiting.
119
What is CD11c a marker for?
monocytes
120
What symptom is seen in about 1/3 of thyomas?
myasthenia gravis
121
What type of infections do people with multiple myeloma have difficulty fending off?
encapsulated bacteria.
