Chapter 6: White blood cell disorders Flashcards
1
Q
neoplastic proliferation of blasts; defined as the accumulation of greater than 20% of blasts in bone marrow
A
acute leukemia
2
Q
blasts “crowd out” normal hematopoiesis resulting in anemia (fatigue), thrombocytopenia (bleeding), and neutropenia (infection).
A
acute leukemia
3
Q
high or low WBC in acute leukemia?
A
high (blasts are large, immature cells, with punched out nucleoli
4
Q
ALL
A
Acute lymphoblastic Leukemia (a sub-division of acute leukemia)
5
Q
AML
A
acute myelogenous leukemia (a sub-division of acute leukemia)
6
Q
neoplastic accumulation of LYMPHOblasts (>20%) in the bone marrow
A
ALL
7
Q
Upon diagnostic testing, TdT positive nuclear staining is detected in an immature cell
A
ALL
8
Q
TdT
A
a DNA polymerase found only in immature lymphobasts
9
Q
very common in children. especially those with down syndrome (OLDER than 5)
A
ALL
10
Q
Two types of ALL
A
B-ALL and T-ALL
11
Q
Most common type of ALL
A
B-ALL
12
Q
TdT+ lymphoblasts that express CD10, CD19, and CD20
A
B-ALL
13
Q
requires prophalaxis to scrotum and CSF
A
chemotherapy for B-Acute lymphocytic leukemia
14
Q
cytogenetic abnormalities associated with B-ALL
A
t(12;21) and t(9;22)
15
Q
t(12;21)
A
- good prognosis in B-ALL; usually seen in children
- ETV6 and RUNX1 genes
16
Q
t(9;22)
A
Philadelphia ALL…you are fucked, what songs do you want at your funeral? seen mostly in adults. BCR-ABL genes
17
Q
characterized by lymphoblasts (TdT+) that express markers ranging from CD2-CD8. CD10 is NOT seen.
A
T-ALL
18
Q
Teenagers and thymic mass (mediastinal)
A
T-ALL—>Acute lymphoblastic lymphoma
19
Q
Neoplastic accumulation of immature myeloid cell (>20%) bone marrow
A
AML (acute myeloid leukemia)
20
Q
Positive MPO cytoplasmic staining
A
AML
21
Q
Auer rods (MPO crystal aggregates)
A
AML
22
Q
average age of AML?
A
50-60
23
Q
APL
A
acute promyelocytic leukemia (which is an acute myeloid leukemia which is of course acute leukemia)
24
Q
t(15;17)
A
APL
25
translocation of retinoic acid receptor (RAR) on chr. 17 to chr. 15; RAR disruption blocks the maturation and promyelocytes (blasts) accumulate
t(15;17) in APL
26
increased risk of DIC due to numerous primary granules (auer rods) in promyeloctyes
APL
27
Treatment of APL
ATRA (all-trans-retinoic-acid) which binds the altered RAR receptor and allows for maturation
28
Acute monocytic leukemia
proliferation of monoblasts; lack MPO
29
blasts characteristically infiltrate the GUMS
Acute monocytic leukemia
30
acute megakaryoblastic leukemia
lack MPO, proliferation of megakaryoblasts
31
Associated with down syndrome (except unlike ALL it arises before the age of 5 years old)
ACUTE MEGAKARYOBLASTIC LEUKEMIA
32
arises mainly from pre-existing dysplasia (myelodysplastic syndromes)
AML (acute myeloid leukemia)
33
Increased blast but still under 20%, hypercellular bone marrrow, and cytopenia
myelodisplastic syndrome
34
Neoplastic proliferation of MATURE circulating lymphocytes. characterized by a high white blood cell count
Chronic Leukemia
35
CLL
chronic lymphocytic leukemia
36
Neoplastic proliferation of naive B cells that co-express CD5 and CD20
CLL
37
Most common leukemia overall
CLL
38
Smudge cell
CLL
39
increased lymphocytes and smudge cells are seen in blood smear
CLL
40
Most common cause of death in CLL?
hypogammaglobulinemia (i.e. infection kills them)
41
3 Complications of CLL
1) hypogammaglobulinemia
2) Autoimmune hemolytic anemia
3) Richter transformation
42
Richter transformation
CLL transforms to diffuse large b-cell lymphoma (marked clinically by enlarged lymph node or spleen)
43
SLL
small lymphocytic lymphoma commonly arises from CLL (common lymphocytic leukemia) when involvement of lymph nodes leads to ---> LAD (lymphadenopathy)
44
Hairy Cell Leukemia
neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes.
45
Cells are positive for tartrate-resistant acid phosphatase (TRAP+)
Hairy Cell Leukemia
46
TRAP+ stain, trapped in red pulp (splenomegaly), trapped in bone marrow (LAD absent). Also bone marrow fibrosis (dry tap)
Hairy cell leukemia
47
Treatment for Hairy Cell Leukemia
ADA inhibitor 2-CDA (cladribine)
48
ATLL
Adult T-Cell Leukemia/Lymphoma
49
Neoplastic proliferation of mature CD4+ T-cells
ATLL
50
associated with HTLV-1 (seen in japan and caribbean)
ATLL
51
rash (skin infiltration), LAD, hepatosplenomegaly, lytic bone lesions and hypercalcemia
ATLL
52
Mycosis fungoides
neoplastic proliferation of mature CD4+ t cells that infiltrate the skin, producing localized skin rash, plaques and nodules.
53
Pautrier microabscesses
aggregates of neoplastic cells in epidermis. seen in mycosis fungoides
54
characteristic lymphocytes with cerebriform nuclei (SEZARY CELLS) are seen in blood smear
mycosis fungoides
55
MPD
myeloproliferative disorders
56
- disease of late adulthood (50-60)
- high WBC with hypercellular bone marrow
- neoplastic proliferation of mature cells in myeloid lineage
myeloproliferative disorders
57
MPDs include
- CML (chronic myeloid leukemia)
- PV (polycythemia vera)
- ET (essential thrombocythemia)
- myelofibrosis
58
BASOPHILIA is characteristically seen in
CML (chronic myeloid leukemia)
59
neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors (basophils)
CML
60
BCR -ABL fusion protein with increased tyrosine kinase activity
t(9;22) phili chromosome. seen in CML.
61
Patient with a 9;22 translocation presents to clinic with basophilia and splenomegaly. You are worried his CML is progressing to the accelerated phase of the disease. What are you most worried about ?
Disease progression to AML (2/3 of all cases) or ALL (1/3 of all cases)
62
3 ways to distinguish CML from a leukemoid rxn.
1) Basophilia in CML
2) LAP negative (leukocyte alkaline phosphatase)
3) t(9;22) in CML
63
PV (polycythemia vera)
proliferation of mature myeloid cells, especially red blood cells (granulocytes and platelets also increased)
64
A myeloproliferative disorders associated with a JAK 2 kinase mutation
PV, ET, and myelofibrosis
65
Clinical symptoms of PV are mostly due to
hyperviscosity of the blood
66
Symptoms of PV:
1) blurry vision and head ache
2) increased risk of venous thrombosis
3) plethora (flushed face due to congestion)
4) ITCHING AFTER BATHING (increased histamine and mast cells)
67
Ischemic infarction to liver is seen in Budd-Chiari syndrome. What MPDs most likely caused this syndrome?
PV
68
PV treatment
phlebotomy or second-line hydroxyurea
69
PV must be distinguished from reactive polycythemia. How?
In PV:
- EPO is decreased (not increased like in renal cell carcinoma ectopic EPO reactive polycythemia)
- SaO2 normal
70
Neoplastic proliferation of platelets; RBCs and granulocytes are also increased
ET (essential thrombocythemia)
71
True or false: ET rarely progresses to marrow fibrosis or acute leukemia and has no significant risk for hyperuricemia or gout
TRUE (platelets are simply blebs off of megakaryocytes aka have no nucleus aka no purine degradation)
72
Myelofibrosis
neoplastic proliferation of mature myeloid cells; especially megakaryocytes
73
megakaryocytes produces excess PDGF causing marrow fibrosis
Myelofibrosis
74
Clinical triad of myelofribrosis
1) Splenomegaly (due to extramedullary hematopoiesis...stem cells have migrated back)
2) Leukoerythroblastic smear (tear drop)
3) Increased risk of infection, thrombosis and bleeding
75
when is painful LAD usually occur?
lymph nodes that are draining a region of acute infection (acute lymphadenitis)
76
when does painless LAD usually occur?
- chronic inflammation
- metastatic carcinoma
- lymphoma
77
Follicular hyperplasia (b-cell region) is seen in what?
HIV infection (dedritic cells) or RA
78
paracortex hyperplasia (T-cell region) seen in what?
viral infection (IM)
79
neoplastic proliferation of lymphoid cells that form a mass; may arise in a lymph node or in extranodal tissue
lymphoma
80
NHL
non-hodgkin lymphoma (60% of lymphomas)
81
HL
Hodgkin lymphoma (40% of lymphomas)
82
NHL with small B cells
follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and SLL (remember from CLL)
83
NHL with intermediate sized cells
Burkitt lymphoma
84
NHL with Large B cells
Diffuse large B-cell lymphoma (DLBCL)
85
malignant cells of hodgkin lymphoma
reed-sternberg cells
86
malignant cells of NHL
lymphoid cells
87
reed-sternberg cell composition
reactive cells (inflammatory cells and fibrosis)
88
painless LAD usually arises late in life
NHL
89
Painless LAD occasionally with "B" symptoms, usually arise in young adults (female)
HL
90
Neoplastic proliferation of small B cells (CD20+) that form follicle like nodules
Follicular lymphoma
91
driven by t(14;18)
follicular lymphoma
92
t(14;18)
- follicular lymphoma
| - BCL2 on 18 translocates to the IgHeavy chain locus on chromosome 14. Anti-apoptotic upregulated.
93
rituximab is an anti-CD20 antibody used to treat
follicular lymphoma
94
Follicular lymphoma can progress to
diffuse large b-cell lymphoma (presents as an enlarging lymph node)
95
lack tingle body macrophages in germinal centers
follicular lymphoma
96
Bcl2 expression in follicule
follicular lymphoma
97
mantle cell lymphoma
proliferation of small b-cells (CD20+) that expands the mantle zone
98
t(11;14)
Mantle cell lymphoma
99
Driven by t(11;14). Explain
Mantle cell lymphoma; Cyclin D1 (G1-->S) gene on 11 translocates to 14 IgHeavy. Upregulated. facilitates neoplastic proliferation.
100
Marginal zone lymphoma (remember this is still a NHL)
proliferation of small b-cells (CD20+) that expands the marginal zone
101
marginal zone is formed by ?
post-germinal b-cells (memory b-cells)
102
An NHL associated with H.pylori gastritis, hashimoto thyroiditis, sjogren syndrome
Marginal zone lymphoma
103
MALToma
marginal zone lymphoma in mucosal sights
104
Gastric MALToma may regress with treatment of ...
H. Pylori
105
Neoplastic proliferation of inter-mediate sized b-cells (CD20+); associated with EBV and classically presents as an extranodal mass in a child or young adult
Burkitt Lymphoma
106
African form of Burkitt lymphoma involves...
the jaw
107
sporadic form of Burkitt lymphoma usually involves ...
abdomen
108
driven by t(8;14). Explain
- Burkitt lymphoma
- C-myc on 8 translocates to IgHeavy on 14
- overexpression of c-myc oncogene promotes cell growth
109
characterized by high mitotic index and starry-sky appearance on microscopy
Burkitt lymphoma
110
most common form of NHL?
Diffuse Large B-Cell Lymphoma
111
neoplastic proliferation of diffuse large b-cells (CD20+) that grow diffusely in sheets. clinically aggressive / high grade
Diffuse Large B-Cell Lymphoma
112
arises sporadically or from transformation of low-grade lymphoma (follicular lymphoma)
Diffuse Large B-Cell Lymphoma
113
Reed-Sternberg (RS) cells are what? and are usually positive for what?
Hodgkin Lymphoma: large B-cells with multi-lobed nuclei and prominent nucleoli (owl-eyed); classically CD15+ and CD30+
114
RS cells secrete cytokines resulting in B symptoms which include
fever, chills, weight loss, and night sweats
115
Reactive inflammatory cells make up a bulk of the tumor and form the basis for classification of HL. Subtypes include:
Nodular sclerosis
Lymphocyte-rich
Lymphocyte-depleted
Mixed Cellularity
116
most common for of HL
Nodular sclerosis (70%)
117
presents as enlarging cervical or mediastinal lymph node in young adult, usually female. Lymph node is divided by a band of sclerosis
Nodular sclerosis HL
118
RS cells present in lake-like spaces (lacunar cells)
Nodular sclerosis HL
119
Best prognosis of HL subtypes
lymphocyte rich HL
120
Eosinophila seen in what?
Mixed Cellularity HL
121
RS cells produce what resulting in eosinophila in mixed cellularity HL
IL-5
122
What is the most aggressive subtype of HL (hint: it is usually seen in the elderly and HIV positive individuals)
Lymphocyte-depleted
123
Dyscrasias
plasma cell disorders
124
multiple myeloma, MGUS, and waldenstrom macroglobulinemia are examples of
plasma cell disorders
125
malignant proliferation of plasma cells in bone marrow
multiple myeloma
126
most common primary malignancy of bone
multiple myeloma
127
High serum IL-6 may be present in what? what does IL-6 do?
- multiple myeloma
| - IL-6 stimulates plasma cell growth and immunoglobulin production
128
Multiple Myeloma clinical features
see page 63 of pathoma
129
MGUS
Monoclonal gammopathy of undetermined significance
130
increased serum M spike on SPEP; other features of multiple myeloma are absent: no lytic bone leason, hypercalcemia, AL amyloid, or Bence Jones proteinuria)
MGUS
131
B-cell lymphoma with monoclonal IgM production
Waldenstrom Macroglobulinemia
132
Increased serum protein M-spike (comprised of IgM). Generalized LAD with no lytic bone lesions.
Waldenstrom Macroglobulinemia
133
Visual and neurologic deficits (retinal hemorrhage or stroke)--IgM pentamer is large and causes serum hyperviscosity--> defective platelet aggregation-->bleeding
Waldenstrom Macroglobulinemia
134
treatment for Waldenstrom Macroglobulinemia
plamaspheresis
135
neoplastic proliferation of langerhan cells
langerhans cell histiocytosis
136
What are langerhan cells?
--> specialized dendritic cells founds predominantly in the skin (derived from bone marrow monocytes). They present antigen to naive T-cells.
137
Langerhans cell histiocytosis diseases (3)
- Letter-Swiwe Disease
- Eosinophilic granuloma
- Hand-Schuler-Christain disease
138
Characteristic birbeck (tennis racket) granules seen on electron microscopy.
Langerhans cell histiocytosis
139
CD1a+ and S100+
Langerhans cell histiocytosis
140
- malignant proliferation of langerhans cells
| - classic presentation is skin rash and cystic skeletal defects in an infant (
Letter-Swiwe Disease
141
Benign proliferation of langerhans cells in bone. Classic presentation is pathologic fracture in adolescent.
Eosinophilic Granuloma
142
Malignant proliferation of langerhans cells. Classic presentation of is scalp rash, lytic skull defects, diabetes insipidus, and exophthalmos in a child.
Hand-Schuler-Christain Disease
143
Name four chronic leukemias
- CLL
- Hairy Cell Leukemia
- ATLL
- Mycosis Fungoides
144
In mycosis fungoides neoplastic mature CD4+ T-cells can aggregate in the epidermis to produces Pautrier microabscesses or can spread to involve the blood, producing _______ _________.
Sezary Syndrome
145
what cancers have to capability of progressing to DLBCL?
CLL and follicular lymphoma
146
Co-expression of CD10, CD19, and CD20 are seen in what two cancers? how do you tell them apart?
- B-ALL and Follicular lymphoma and Burkitt lymphoma
- Follicular lymphoma is Bcl2+ and B-ALL is TdT+
- Burkitt lymphoma t(8;14) (increased c-myc)
147
Co-expression of CD5, CD20 (CD19) is seen in what two cancers? How do you tell them apart?
- Mantle Cell lymphoma and CLL
- CLL is usually CD23+ (also look for smudge cells)
- Mantle is CD23- and Cyclin D1+ with possible lymphomatoid polyposis (GI)
- MANTLE= surface light chain restriction BRIGHT
- CLL/SLL= surface light chain restriction DIM
148
increased small mature lymphs with hyperclumped nuclear chromatin (soccer ball cells) and smudge cells
CLL/SLL
149
The following are buzzwords for ________ _______? :
| "Spreads in a contiguous fashion" ; "Reed-Sternberg Cell" ; "bimodal"
HL
150
EBV can be associated with what three cancers?
Hodgkin Lymphoma, DLBCL, and Burkitt Lymphoma
