Hematologic Malignancies Flashcards
(45 cards)
1
Q
List three viruses known to have oncogenic roles in some cases of lymphoma
A
- Epstein-Barr virus (EBV): Some cases of classical Hodgkin lymphoma, some cases of Burkitt
lymphoma, some other B cell non-Hodgkin lymphomas - Human T cell leukemia virus-1 (HTLV-1): Causative factor in adult T cell leukemia/lymphoma (ATLL)
- Kaposi sarcoma herpesvirus/Human herpesvirus-8 (KSV/HHV-8): Primary effusion lymphoma
2
Q
List the basic functional categories for hematologic malignancies
A
ACUTE LEUKEMIAS MYELODYSPLASTIC SYNDROME (MDS) MYELOPROLIFERATIVE NEOPLASMS (MPNs) NON-HODGKIN LYMPHOMA CLASSICAL HODGKIN LYMPHOMA (CHL) PLASMA CELL NEOPLASMS
3
Q
Genetic Markers of Immaturity
A
CD34
4
Q
Common Lymphoblast Marker (not on mature lymphocytes)
A
TdT
5
Q
Markers of B Cell Lineage
A
CD19
CD22
6
Q
Markers of T Cell Lineage
A
CD3
CD7
7
Q
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A
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8
Q
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A
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9
Q
Generic Marker of Immaturity
A
CD34 (lymphoblasts and myeloblasts)
used in ALL diagnosis
10
Q
Common Lymphoblast Marker (not on mature lymphocytes)
A
Tdt
used in ALL diagnosis
11
Q
B-lineage antigens
A
CD19, CD22, and/or CD79a
12
Q
T-lineage antigens
A
CD2, CD3, CD7
may express CD4 and CD8 (both, one, or neither)
CD99, CD1a (immature T cells only eg T-lymphoblasts)
13
Q
Myeloblast markers…
A
CD117 (C-kit), myeloperoxidase (myeloid antigens)
14
Q
t(8;21)(q22;q22)
A
AML - RUNX1-RUNX1T1
relatively good prognosis
15
Q
inv(16)(p13.1;q22) or t(16;16)(p13.1;q22)
A
AML - CBFB-MYH11
relatively good prognosis
16
Q
t(15;17)(q22;q12)
A
AML - PML-RARA
good prognosis w/ all-trans retinoic acid (ATRA), in combination with arsenic salts
17
Q
t(1;22)(p13;q13)
A
AML - RBM15-MKL1
Relatively good prognosis with intensive chemotherapy
18
Q
abnormalities of 11q23
A
AML - MLL poor prognosis B-ALL - MLL poor prognosis t-AML - MLL (causes abnormalities) very poor prognosis
19
Q
t(9;22)(q34;q11.2)
A
B-ALL - BCR-ABL1
Philadelphia chromosome
worst prognosis of any subtype of ALL
20
Q
t(12;21)(p13;q22)
A
B-ALL - ETV6-RUNX1
very favorable prognosis
21
Q
List three molecular markers currently used to predict prognosis in patients with AML with normal karyotype
A
FLT3 ITD
NPM1
CEBPA
22
Q
List the two main features that characterize myelodysplastic syndrome (MDS)
A
a) ineffective hematopoiesis
b) increased risk of transformation to acute myeloid leukemia
23
Q
Philadelphia chromosome - What gene and disease?
A
BCR-ABL1 - t(9;22)(q34;q11.2)
CML (p210)
Also found in ALL (p190)
24
Q
RARA - What gene and disease? Treatment?
A
t(15;17)(q22;q12)
AML aka PML (Acute promyelocytic leukemia)
all-trans retinoic acid (ATRA), in combination with arsenic salts
25
List three possible negative end points for MPNs.
a) transformation to acute leukemia (usually AML, but sometimes ALL) (in the setting of a prior MPN, transformation to acute leukemia is often referred to as blast phase)
b) development of myelodysplasia with ineffective hematopoiesis (transform to MDS)
c) excessive marrow fibrosis with resultant bone marrow failure
26
Four MPNs
1) Chronic Myelogenous Leukemia (CML)
2) Polycythemia vera (PV)
3) Primary Myelofibrosis (PMF)
4) Essential Thrombocythemia (ET)
27
Basic Classification of MDS? (2)
~ Low grade MDS: Myeloblasts account for less than 5% of marrow cells, and less than 2% of peripheral blood cells
~ High grade MDS: Myeloblasts account for 5% or more of marrow cells, and/or 2% or more of peripheral blood cells
28
Common Themes in MPNs
1) Early disease characterized by increase in one or more blood cell types, with corresponding increase in marrow cellularity
2) Patients often have splenomegaly and/orbhepatomegaly
3) Usually have insidious onset
4) Without treatment, progress to….
- excessive marrow fibrosis with resultant bone marrow failure
- transformation to acute leukemia (much less common for MPNs than for MDS)
29
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Chronic Myelogenous Leukemia (CML)
Type of Hemato Malignancy?
Gene?
Main manifestation?
Phases?
```
- MPN
- (9;22)(q34;q11.2) - BCR-ABL1 gene fusion (Philadelphia chromosome)
- prominent neutrophilic leukocytosis
- night sweats, weight loss, splenomegaly, and anemia
- chronic phase: blasts not significantly increased, no dysplasia
- blast phase (essentially transformation to acute leukemia)
- PTKIs: imatinib (Gleevec) (inhibits protein)
- second generation PTKI for CML, dasatinib
30
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Polycythemia vera (PV)
Type of Hemato Malignancy?
Gene?
Main manifestation?
Serious complications?
Treatment?
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- MPN
- increase in RBC mass (erythrocytosis), usually accompanied by increased neutrophils and platelets, and with the bone marrow showing trilineage hyperplasia, bizarre megakaryocytes
- activating mutation of JAK2, usually a V617F point mutation
- headaches, dizziness, possibly hepatosplenomegaly
- serious complications: thrombosis
- serial phlebotomy
31
Primary Myelofibrosis
Type of Hemato Malignancy?
Gene?
Main manifestation?
- MPN
- proliferation of the granulocytic and megakaryocytic lineages, with eventual progression to myelofibrosis (thus, it's very similar to PV, but lacks the erythrocytosis)
- Leukoerythroblastosis
- organomegaly
- maybe teardrop
- Mutations of JAK2 can be found in around 50% of cases
32
Essential Thrombocythemia (ET)
Type of Hemato Malignancy?
Gene?
Main manifestation?
- MPN
- marked thrombocytosis
- no granulocytic hyperplasia
- megakaryocytes large and bizarre
- Mutations of JAK2 can be found in around 50%
- thrombosis of major arteries or veins
- hepatosplenomegaly NOT common
33
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
- NHL
- Definition: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are B-cell lymphomas. CLL and SLL are essentially the same disease, the only difference being where the cancer primarily occurs.
- monoclonal mature B cells; lymphocytosis
- Immunophenotype:
Positive: CD5, CD23, CD19
Weak: CD20, surface immunoglobulin, CD22, CD11c
Negative: CD10, FMC7
- Genetic: Deletion of 13q14: the most common genetic alteration, in >50% of CLL, favorable prognosis
Deletion of 11q22-q23: in ~ 20% of CLL
34
Follicular Lymphoma (FL)
- NHL
- A lymphoma of germinal center B cells (centrocytes and centroblasts) with typically at least a partially follicular pattern
- Follicles: Closely packed, back to back, with effacement of the nodal architecture
- Two type of tumor cells, predominantly centrocytes in most cases: Centrocytes, Centroblasts
- B-cell markers positive: CD19+, CD20+
BCL2+ positive
Germinal center B-cell marker positive: CD10 and BCL6
- t(14;18)(q32;q21) overexpression of BCL2
35
Mantle Cell Lymphoma (MCL)
- NHL
- A B-cell neoplasm composed of monomorphic small to medium-sized lymphocytes with irregular nuclei that morphologically resemble centrocytes but often have slightly less irregular nuclear contours
- effacement of lymph node by a monomorphic lymphoid proliferation with a vaguely nodular, diffuse or mantle zone growth pattern
- B-cell markers positive: CD19+, CD20+
CD5 positive, CD23 negative
Cyclin D1 (BCL1) positive
Germinal center B-cell marker positive: CD10 and BCL6
- t(11;14)(q13;q32), involving BCL1 gene on 11q13 and IGH gene on 14q32
36
Burkitt ’s lymphoma (BL)
- NHL
- A highly aggressive B-cell lymphoma, often presenting at extranodal sites or as a leukemic form. The tumor is typically composed of monomorphic, medium-sized Bcells with basophilic cytoplasm and a high mitotic rate.
- monomorphic, medium-sized cells with starry sky pattern
- B-cell markers positive: CD19+, CD20+
High proliferation index, nearly 100% by Ki-67 staining
EBV mostly positive in endemic BL, and ~30% positive in sporadic andimmunodeficiency-associated BL
Negative: BCL2, CD5, CD23, TdT
- Most cases have a characteristic translocation, t(8;14)(q24;q32), which juxtaposes the
MYC gene at 8q24 next to IGH@ at 14q32
37
BCL2
- Major function: to suppress apoptosis
| - BCL2 gene is down-regulated in the normal germinal center B-cells
38
Cyclin D1 (BCL1)
- Release of E2F1–3 transcription factors, which activate genes that are required for cell-cycle progression > G1/S transition and cell divides
39
MYC
- regulator gene that codes for transcription factor
40
Major Subtypes of Hodgkin's Lymphoma
1) Nodular sclerosis classical Hodgkin's lymphoma
2) Lymphocyte-rich classical Hodgkin's lymphoma
3) Mixed cellularity classical Hodgkin's lymphoma
4) Lymphocyte-depleted classical Hodgkin's lymphoma
41
What are 4 Plasma Cell Neoplasms?
1) Plasma Cell Myeloma (PCM, or Multiple Myeloma)
2) Monoclonal Gammopathy of Undetermined Significance (MGUS)
3) Solitary plasmacytoma of bone
4) Extraosseous Plasmacytoma
42
Plasma Cell Myeloma (PCM, or Multiple Myeloma)
- Plasma Cell Neoplasm
Definition: a bone marrow–based, multifocal plasma cell neoplasm associated with an M protein in serum or urine. PCM originates from the marrow with disseminated marrow involvement in most cases.
- bone pain in the back or extremities due to lytic lesions or osteoporosis. Weakness and tiredness, often related to anemia, are common complaints
43
Monoclonal Gammopathy of Undetermined Significance (MGUS)
- Plasma Cell Neoplasm
- presence of a monoclonal immunoglobulin in the serum or urine of a patient with no evidence of plasma cell myeloma
- precursor lesion of PCM
44
Solitary plasmacytoma of bone
- Plasma Cell Neoplasm
- a localized tumor of the bone, which is
composed of clonal plasma cells that are cytologically, immunophenotypically, and genetically similar to those of plasma cell myeloma
- Single bone lesion consisting of monoclonal plasma cells
45
Extraosseous Plasmacytoma
- Plasma Cell Neoplasm
- localized plasma cell tumors that arise in tissues outside of the bone marrow. - They appear to be biologically distinct from solitary plasmacytoma of bone and plasma cell myeloma.
- present as localized mass lesions. About 75% of them
occur in the upper respiratory tract, including nasal passages, sinuses, oropharynx, and larynx.
