WBC pathology Flashcards
1
Q
● Disorders of white blood cells can be classified
into two broad categories:
A
● Proliferative disorders (↑ WBC Count)
● Leukopenia
2
Q
○ Deficiency of leukocytes
A
Leukopenia
3
Q
Ref val
white cells
A
4.8-10.8
4
Q
Ref val
Granulocytes
A
40-70
5
Q
Neutrophils
A
1.4-6.5
6
Q
Lymphocytes
A
1.2-3.4
7
Q
Monocytes
A
0.1-0.6
8
Q
Eosinophils
A
0-0.5
9
Q
○ Refers to an increase in the number of
white cells in the blood
A
Leukocytosis
10
Q
● Peripheral blood leukocyte count is influenced by
several factors:
A
● 1.Size of myeloid and lymphoid precursor and
storage cell pools in the bone marrow, thymus,
circulation, peripheral tissues.
● 2.Rate of release of cells from the storage pools
into the circulation
● 3.Proportion of cells that are adherent to blood
vessel walls at any time (marginal pool)
● 4.Rate of extravasation of cells from blood to
tissues.
11
Q
■ B-cell, T-cell and NK-cell origin
■ Lymphocyte class or stage of
maturation
A
Lymphoid neoplasms
12
Q
■ Arise from early hematopoietic progenitors
A
Myeloid neoplasms (Segmented or Granular lymphocytes)
13
Q
immature progenitor cells
accumulate in the BM
A
Acute myeloid leukemias (AML)
14
Q
associated with infective
hematopoiesis and resultant peripheral blood cytopenias
A
Myelodysplastic syndromes (MDS) -
15
Q
increase production of one or more
differentiated myeloid elements
usually leads to elevated peripheral
blood counts
A
■ Myeloproliferative neoplasms -
16
Q
➢ Chronic myeloid leukemia
(CML) falls under
A
Myeloproliferative neoplasms -
17
Q
■ Macrophages and dendritic cells ■ A special type of immature dendritic cell, the Langerhans cell, gives rise to a spectrum of neoplastic disorders referred to as the Langerhans cell histiocytoses.
A
○ Histiocytes
18
Q
When there is mutation of the tyrosine kinase or
MYC translocation, then there is
A
a gain of function.
19
Q
INHERITED GENETIC FACTORS
A
Bloom syndrome, Fanconi anemia, and ataxia telangiectasia (acute leukemia or lymphoma)
Down syndrome (trisomy 21) and type 1 neurofibromatosis
20
Q
○ Associated with nasopharyngeal
carcinoma
○ Burkitt lymphoma, Hodgkin lymphoma
(HL), B cell lymphomas
A
EBV
21
Q
Kaposi sarcoma
herpesvirus)
○ Malignant effusion
A
Human herpesvirus-8
22
Q
IATROGENIC FACTORS
A
Chemotherapy - Myeloid and lymphoid
neoplasms
23
Q
SMOKING
● AML increased
A
1.3 to 2 fold in smokers
24
Q
○ Neoplasms that present widespread
involvement of the bone marrow and the
peripheral blood
A
Leukemia
25
LYMPHOID NEOPLASMS
Leukemia
Lymphoma
Plasma cell neoplasms
NHLs and Hodgkin lymphomas
26
Proliferations of white cells, typically
lymphocytes, that usually present as
discrete tissue masses
Lymphoma
27
Two types of Lymphoma:
○ Hodgkin lymphoma
| ○ Non-Hodgkin lymphomas (NHL)
28
○ Most often arise in the bone marrow and
only infrequently involve lymph nodes or
the peripheral blood
● Plasma cell neoplasms
29
○ Enlarged nontender lymph nodes (often
>2cm)
○ Extranodal sites (skin, stomach or brain)
NHLs and Hodgkin lymphomas
30
Suppression of normal
| hematopoiesis by tumor cells in the bone marrow
Lymphocytic leukemias
31
Neoplasm of Reed-Sternberg cells and variants
Hodgkin’s Lymphoma
32
Most lymphoid neoplasms resemble some
| recognizable stage of
B- or T-cell
differentiation
○ 85-90% of lymphoid neoplasms are of B-cell origin
33
```
T or F
Individuals with inherited or acquired
immunodeficiency are at high risk of
developing certain lymphoid neoplasms,
particularly those caused by oncogenic
viruses
```
T
34
PRECURSOR T AND B CELL NEOPLASMS
ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA
35
● Neoplasms composed of immature B (pre-B) or T
(pre-T) cells joined together because they show
similar tumor called lymphoblasts
● Manifest as childhood acute leukemias
ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA
36
o About 85%
o childhood acute leukemia
o uncommonly presents as a mass in the skin
or a bone
● B-ALL
37
o Less common
o Present in adolescent males as thymic
lymphomas (thymic mass)
T-ALL
38
is the most common cancer of children
ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA
39
o B-ALL peaks at
age 3
40
T-ALL peak in
adolescent
41
▪ Number of normal bone marrow preB cells (cell of origin) is greatest very
early in life
3
42
T-ALLs - mutations in
NOTCH1 (essential for T-cell development)
43
B-ALLs - mutations in
PAX5, TCF3, ETV6, and
RUNX1 (genes required for proper differentiation of
early hematopoietic precursors)
44
Most common numerical or structural chromosomal changes
hyperploidy (>50
| chromosomes)
45
T or F
| Hyperploidy has a better prognosis than hypodiploidy
seen only in B-ALL
T
46
Definitive diagnosis relies ________performed
| with antibodies specific for B- and T-cell antigens
on stains
47
Lymphoblasts are myeloperoxidase- (negative or positive)
negative
48
T or f
Lymphoblasts are myeloperoxidase-negative and
contain Periodic Acid-Schiff-positive cytoplasmic
material
T
49
Immunostaining for terminal deoxynucleotidyl
transferase (TdT), a specialized DNA polymerase that is expressed only in pre-B and pre-T lymphoblasts is
positive in >95% of cases
IMMUNOPHENOTYPE
50
express the pan B-cell marker CD19
| and the transcription factor PAX5 as well as CD10
Lymphoblasts
51
In very immature B-ALLs, CD10 is
negative
52
More mature “late pre-B” ALLs express
CD10, 19, 20,
| and cytoplasmic IgM heavy chain (μ chain)
53
● Characteristics of ALL are the ff:
1. Abrupt stormy onset with days to few weeks of
the first symptoms
2. Symptoms related to depression of marrow
function (o Fatigue due to anemia; Fever)
3. Mass effects caused by neoplastic infiltration
(more common in ALL) including: Bone pain, lymphadenopathy,
splenomegaly, and hepatomegaly; testicular enlargement, Compression syndrome)
4. Central nervous system manifestations
54
- patient
is very red, rhetoric and
congested
Compression syndrome
55
Factors associated with worse prognosis:
1. Age younger than 2 years
● strong association of infantile ALL with
translocations involving the MLL gene
2. Presentation in adolescence or adulthood
3. Peripheral blood blast counts >100,000
● reflects a high tumor burden
56
Favorable prognostic markers include:
```
● age 2-10 years
● low WBC count
● hyperploidy
● trisomy of chromosomes 4, 7 & 10
● presence of a t(12;21)
o translocation of 12;21
```
57
PERIPHERAL B-CELL NEOPLASMS
CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL
LYMPHOCYTIC LYMPHOMA
FOLLICULAR LYMPHOMA
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)
58
```
Chronic lymphocytic leukemia (CLL) and small
lymphocytic lymphoma (SLL) differ only in the
```
degree of peripheral blood lymphocytosis
59
Most affected patients have sufficient lymphocytosis
| to fulfill the diagnostic requirement for CLL
absolute lymphocyte count >5000/mm3
60
s the most common leukemia of adults in
| the Western world
CLL
61
The median age at diagnosis is __years, and there is a 2:1 male predominance
60
62
T or F
CLL/SLL is much less common in Japan and other Asian countries than in the West
T
63
In CLL/SLL, Most common genetic anomalies are deletions of
13q14.3, 11q, and 17p and trisomy 12q
64
Molecular characterization of the region deleted on
| chromosome 13 has implicated
2 microRNAs, miR-15a and miR-16-1, tumor suppressor genes
65
Loss of these mIRs is believed to result in
overexpression of the anti-apoptotic protein BCL2, which is uniformly observed in CLL/SLL
66
CLL/SLL morphology
Lymph nodes are diffusely effaced (being replaced) by
predominantly small lymphocytes 6 to 12 μm in
diameter with round to slightly irregular nuclei,
condensed chromatin, and scant cytoplasm
67
are pathognomonic for CLL/SLL
Proliferation centers
Admixed are variable numbers of larger activated lymphocytes that often gather in loose aggregates referred to as proliferation centers that contain mitotically active cells
68
a larger cell with a centrally placed nucleolus,
prolymphocyte
69
CLL/SLL
A characteristic finding is the presence of
disrupted tumor cells (smudge cells)
70
Tumor cells express the pan B-cell markers
CD19 and CD20, as well as CD23 and CD5
71
eukopenia can be seen in individuals with
SLL
72
is common and
contributes to an increased susceptibility to
infection, particularly those caused by bacteria
10% to 15% of patients develop hemolytic anemia
or thrombocytopenia due to autoantibodies made
by nonneoplastic B cells
Hypogammaglobulinemia
73
CLL/SLL
Other variables that correlate with a worse
outcome include:
○ The presence of deletions of 11q and 17p
(the latter involving TP53)
○ A lack of somatic hypermutation
○ The expression of ZAP-70, a protein that augments signals produced by the Ig
receptor
○ The presence of NOTCH1 mutations
74
Transformation to diffuse large B-cell
| lymphoma (DLBCL) so-called
Richter
syndrome (approximately 5% to 10% of
patients)
75
often heralded by the
development of a rapidly enlarging mass
within a lymph node or the spleen
Richter
| syndrome
76
● Most common form of indolent NHL
● It affects 15,000 to 20,000 individuals per year
● Presents in middle age and afflicts males and females
equally
● Less common in Europe and rare in Asian
populations
FOLLICULAR LYMPHOMA
77
is strongly associated with
| chromosomal translocations involving BCL2.
FOLLICULAR LYMPHOMA
78
● Hallmark is a (14;18)
● Translocation that juxtaposes the IGH locus on
chromosome 14 and the BCL2 locus on chromosome
18.
FOLLICULAR LYMPHOMA
79
Antagonizes apoptosis and promotes the
| survival of follicular lymphoma cells
BCL2
80
is characteristically devoid of apoptotic cells
Follicular lymphoma
81
encodes a histone methyltransferase,
suggesting that epigenetic abnormalities such as
changes in the patterns of histone marks have an
important role in this neoplasm.
KMT2D
