Myeloid Neoplasms I Flashcards
(45 cards)
1
Q
what are the four main categories of myeloid neoplasms?
what are the defining characteristics of category?
A
- myeloproliferative neoplasms (MPN)
- effective hematopoiesis with increased production → cells (both mature & immature) released into blood, thus
- increased peripheral blood counts
- effective hematopoiesis with increased production → cells (both mature & immature) released into blood, thus
- myelodysplastic syndromes (MDS)
-
ineffective hematopoiesis: abnormal cell maturation → cells die before release into peripheral blood, thus:
- cytopenia
-
ineffective hematopoiesis: abnormal cell maturation → cells die before release into peripheral blood, thus:
- MPN / MDS syndromes:
- overlapping MPN & MDS characteristics
- acute myeloid leukemias (AML)
- accumulation of immature myeloid forms in marrow → normal hematopoiesis suppression, thus
- cytopenia
- accumulation of immature myeloid forms in marrow → normal hematopoiesis suppression, thus
2
Q
neoplasms within which four myeloid neoplasm categories result in cytopenia?
A
- MDS (MPN / MDS if MDS predominant)
- AML
3
Q
contrast myeloid neoplasms within the MPN and MDS categories based on
- efficacy of hematopoiesis
- bone marrow status
- peripheral blood cell status
- presence of dyspoiesis
- presence of organomegally
A
both: bone marrow hypercellularity
MPN
- hematopoiesis effective
- increases in peripheral blood counts (both mature + immature)
- no dyspoiesis except for megakaryocytes
- organomegally common
MDS
- hematopoiesis ineffective
- decreases in peripheral blood counts (cytopenia)
- dyspoiesis in 1+ blood lines
- organomegally uncommon
4
Q
neoplasms in each in each myeloid neoplasm category have what in common?
A
= MPN, MDS, MPN/MDS, AML
- involve some loss of regulation
- involves bone marrow + blood & maybe secondary lymphoid tissues
-
can ALL progress to AML:
- suppression of hematopoiesis → peripheral blood cytopenias
5
Q
what are the general features of chronic myeloproliferative neoplasms (MPN)? note:
- pathogenesis
- blood marrow status
- peripheral blood status
- key manifestations
A
- pathogenesis: loss of regulation d/t tyrosine kinase abnormalities → factor-independent proliferation
- maturation / differentiation = normal
- bone marrow:
- hypercellular
- no dyspoesis EXCEPT megakaryocytes*
- peripheral blood status:
- increased cell counts with one type predominating → granulocytes m/c
- manifestations: organomegally (spleen, hepato)
6
Q
list the major types of chronic myeloproliferative neoplasms (MPNs)
A
- chronic myelogenous leukemia (CML)
- polycthemia vera
- primary myelofibrosis
- essential thrombocytosis (ET)
7
Q
chronic myelogenous leukemia (CML) - pathogenesis
A
type of MPN.
- like all MPNs, characterized by tyrosine kinase overactivity d/t defect.
- defect: abnormal chromosome 22 (Ph chromosome). results in
- a t(9,22) recipricol translocation - specifically, translocation of ABL gene (on chromosome 9) to BCR region of chromosome 22, producing BCR-ABL fusion gene.
- the resulting BCR-ABL protein is a constitutively active tyrosine kinase, which leads to uncontrolled proliferation of myeloid progenitors:
- granulocytes > megakaryocytes
- the resulting BCR-ABL protein is a constitutively active tyrosine kinase, which leads to uncontrolled proliferation of myeloid progenitors:
- a t(9,22) recipricol translocation - specifically, translocation of ABL gene (on chromosome 9) to BCR region of chromosome 22, producing BCR-ABL fusion gene.
- defect: abnormal chromosome 22 (Ph chromosome). results in
8
Q
chronic myelogenous leukemia (CML) - comprehensive presentation
A
= type MPN
- divided into 3 stages of presentation:
- chronic phase
- accelerated phase
- blast phase
- overall findings:
- peripheral blood
- increased counts of
- granulocytes ALWAYS (specifically, basophils)
- +/- megakaryocytes,
- NOT RBCS!!
- increased counts of
- bone marrow
- no dyspoesis apart from megakaryocytes → dwarf megakaryocytes (hypolobulated)
- clinical
- splenomegaly common
- NO lymphadenopathy
- anemia sx: pallor, tachy / spnea (RBC suppression)
- hyperuricemia → gout
- bleeding OR thrombus depending on platelet #
- peripheral blood
9
Q
chronic myelogenous leukemia (CML) - chronic phase. how does of the bone, blood and clinical presentation of CML appear during this phase?
A
= type of MPN
- peripheral blood
- increased counts of
-
granulocytes:
- BASOPHILS INVARIABLY.
- eosinophils commonly
- +/- megakaryocytes,
- NOT RBCS!!
-
granulocytes:
- blasts normal (< 2%)
- increased counts of
- bone marrow
- hypercellular
- +/- marrow reticulin fibrosis
- no dyspoesis apart from megakaryocytes
- dwarf megakaryocytes (hypo-lobulated)
- blasts normal (<5%)
- presence of Psuedo-Gaucher cells
- clinical
- splenomegaly common
- NO lymphadenopathy
- anemia sx: pallor, tachy / spnea (RBC suppression)
- hyperuricemia → gout
- bleeding (thrombocytopenia) OR thrombus (thrombyocytosis) depending on platelet #
10
Q
chronic myelogenous leukemia (CML) - accelerated phase: how does of the bone, blood and clinical presentation of CML appear during this phase?
A
type of MPN;
overall, appears just like the chronic phase (with worsening sx) except:
- blasts are increased above normal: though < 20% of peripheral blood or bone marrow cells
- definite presence of reticulin fibrosis in bone marrow
11
Q
chronic myelogenous leukemia (CML) - accelerated phase: how does of the bone, blood and clinical presentation of CML appear during this phase?
A
type of MPN:
overall, appears just like the chronic phase (with worsening sx) except:
- blasts are increased over >20% of the peripheral blood or bone marrow
- presence of granulocytic sarcoma: collections of malignant blasts cells
12
Q
describe the presence of blast cells during each phase of chronic myelogenous leukemia (CML)
A
CML = type of MPN.
- chronic phase: blasts normal
- peripheral blood: < 2%
- bone marrow: < 5%
- accelerated phase: blasts abnormal but < 20% of peripheral blood or bone marrow
- blast phase: blasts > 20% of peripheral blood or bone marrow → can form granulocytic sarcoma
13
Q
A
abnormally large “buffy coat”: layer of leukocytes comprosing the tope of centrifuged peripheral blood
seen in CML: first during the chronic phase
14
Q
A
dwarf megakaryocytes: hypo-lobulated nuclei
CML (type of MPN) - first seen in chronic phase.
15
Q
A
BM aspirate smear showing blast cells > normal but under 20%
CML (type of MPN) - accelerated phase.
16
Q
A
bone marrow with blast cells > normal but under 20%
CML (type of MPN) - accelerated phase.
17
Q
A
pseudo-gaucher cell: sea-blue histiocytes
seen in CML (type of MPN) first in the chronic phase: d/t increased hemophagocytic activity in response to increased turnover of hematopoietic cells
18
Q
polycythemia vera - pathogenesis
A
= type of MPN.
- like all MPNs, characterized by tyrosine kinase overactivity d/t defect.
- somatic gain of function mutation of JAK-2 VG17-F → unregulated proliferation independent of growth factors (in particular - erythropoietin, which will actually be low d/t negative feedback), resulting in panmyelosis: inc of all myeloid cell lines
- granulocytic
- erythroid
- megakaryocytic
- somatic gain of function mutation of JAK-2 VG17-F → unregulated proliferation independent of growth factors (in particular - erythropoietin, which will actually be low d/t negative feedback), resulting in panmyelosis: inc of all myeloid cell lines
19
Q
polycythemia vera - comprehensive presentation
A
- occurs in three phases
- pre-polycythemic phase
- polycythemic phase
- post-polycythemic (spent) phase
- overall presentation
- bone marrow
- hypercellular - panmyelosis: hyperplasia of all 3 cell lines
- no dypoiesis except for megakaryocytes → hyperlobulated
- extensive reticulen / collagen fibrosis
- tear-drop cells
- peripheral blood
- erythrocytosis + mild granulocytosis /megakaryocytosis that evolves to → cytopenia
- bone marrow
- clinical presentation: largely d/t polycythemia
- plethora (red face)
- HTN / headache / dizziness
- erythromelalgia: paroxysmal severe burning pain in the skin of extremities
- splenomegaly common
20
Q
polycythemia-pre-polycythemic phase: how does of the bone, blood and clinical presentation appear during this phase?
A
= type of MPN
- peripheral blood: mild erythrocytosis (polycythemia)
- usually asymptomatic
21
Q
polycythemia- polycythemic phase: how does of the bone, blood and clinical presentation appear during this phase?
A
= type of MPN
- peripheral blood:
-
borderline / mild erythrocytosis (polycythemia) that results in increased
- RBC
- hemoglobin
- hematocrit
- mild granulocytosis, thrombocytosis
-
borderline / mild erythrocytosis (polycythemia) that results in increased
- bone marrow:
- hypercellular, d/t panmyelosis
- +/- hyper-lobulated megakaryocytes
22
Q
polycythemia- post-polycythemic phase: how does of the bone, blood and clinical presentation appear during this phase?
A
= type of MPN
- peripheral blood: cytopenia
- bone marrow: prominent reticulin / collagen fibrosis
- tear-drop cells
- extramedullary hemopoiesis & splenomegaly
23
Q
what are the findings in the peripheral blood during each phase of polycythemia?
A
- pre-polycythemia: mild erythrocytosis (polycythemia)
- polycythemia: erythrocytosis (polycythemia) that results in increased → RBC, Hb, Hematocrit + mild granulocytosis / thrombocytosis
- post-polycythemia: cytopenia
24
Q
identify picture, note important features
A
hypercellular bone marrow + hyper-lobulated megakaryocytes
polycythemia vera (type of MPN) - polycythemic phase
25
identify picture, note important features
**plethora (red face)** - d/t _polycythemia,_ which causes stagnation of blood flow
seen in polycythemia (MPN) - all phases, more likely as phases progress
26
essential thrombocytosis (ET) - pathogenesis
= type of MPN
* like all MPN, due to _overactivity in tyrosine-kinase_ d/t some defect:
* unlike CML & polycythemia - **no genetic abnormalities specific for** **ET.** it is associated with
* JAK - V617 mutations - in 60%
* CALR - in 20%
* MPL mutations - in 3%
* resulting in cell proliferation independent of growth factors:
* **megakaryocytes** (thrombocytosis \> 450,000)
27
essential thrombocytosis - comprehensive presentation
type of MPN
* peripheral blood
* increased cell count of
* **megakaryocytes:**
* **thrombocytes \> 450,000**
* **are LARGE & hyper-lobulated**
* NOT erythrocytes
* NOT granulocytes
* bone marrow:
* **normal cellularity**
* **absent or minimal reticulin fibrosis**
* **LARGE & hyper-lobuted megakaryocytes**
* **clinical**
* **NO SPLENOMEGALY**
* bleeding or clotting depending on function of thrombocytes
28
identify picture, note important features
peripheral blood smear showing **large,** **hyper-lobulated megakaryocytes + nucleated megkaryocyte fragments**
in ET (type of MPN)
29
bone marrow with **LARGE & hyper-lobulated** megakaryocytes
in ET (type of PMN)
30
primary myelofibrosis - pathogenesis
= type of MPN
* like all MPN, due to _overactivity in tyrosine-kinase_ d/t some defect:
* unlike CML & polycythemia - **no genetic abnormalities specific for** **primary myelofibrosis** it is associated with
* JAK - V617 \> CALR \> MPL
* leads to proliferation independent of growth factors:
* **marrow megakaryocytes**
* +/- granulocytes
* NOT erythrocytes
31
identify picture, note important features
peripheral blood showing **thrombocytopenia** with **large, bizzare platelets** + **many tear-drop cells**
primary myelofibrosis - fibrotic phase
32
bone marrow: **hypocellular** with **reticulin/collagen fibrosis** & **_dilated sinuses_**
primary myelofibrosis - fibrotic phase
33
bone marrow: **hypocellular** with **reticulin/collagen fibrosis** & **_dilated sinuses_**
primary myelofibrosis - fibrotic phase
34
list the pathogenesis of each MPN
all: d/t overactive tyrosine kinase activity
* CML: **BCR-ABL1 fusion gene d/t t9,22 reciprocal translocation**
* polycythemia vera: **JAK2 V617F gain of function** (t9,22 negative)
* ET: **no specific genetic abnormalities**
* associated with
* JAK - V617 \> CALR \> MPL mutations
* primary myelofibrosis: **no specific genetic abnormalities**
* associated with
* JAK - V617 \> CALR \> MPL mutations
35
how does each each MPN affect _erythrocytes?_
* CML: **no erythrocytosis & usually suppressed → anemia**
* polycythemia: **erythrocytosis → cytopenia**
* pre-polycythemia: mild erythrocytosis
* polycythemia: severe erythrocytosis → _inc RBC / Hb / Hct_
* post-polycythemia (spent phase) cytopenia
* ET: **no erythrocytosis (normal)**
* primary myelofibrosis: **no erythrocytosis & usually suppressed (anemia)**
36
how does each MPN affect megakaryocytes?
all 4 types often show megakaryocyte dyspoesis
* peripheral blood:
* CML - _possible_ thrombocytosis
* polycythemia: - _mild_ thrombocytosis
* ET - _severe thrombocytosis_: \> 450,000 platelets, LARGE & hyper-lobulated
* bone marrow:
* CML: **dwarf (hypo-lobulated)** -1st seen in _chronic phase_
* polycythemia: **hyper-lobulated** - 1st seen in _polycythemic phase_
* ET: **LARGE & hyper-lobulated + nucleated megakaryocyte fragments**
* primary myelofibrosis: atypia: **clusters, hyperchromatic nuclei, “cloud like” nuclei**
37
how does each MPN affect granulocytes?
* CML: **invariable, marked granulocytosis → _LEUKOCYTIC AND GRANULOCYTIC LEFT SHIFT_ + _buffy coat_**
* specifically:
* BASOPHILIA ALWAYS
* neutropenia, eosinophilia commonly
* polycythemia: **mild granulocytosis**
* d/t marrow pancytopenia !!
* ET: **no/ mild** **granulocytosis → NO LEFT SHIFT**
* primary myelofibrosis: **no / mild granulocytosis → NO LEFT SHIFT**
38
how does each MPN affect bone marrow in terms of
* cellularity
* fibrosis
* other features
* cellularity
* CML - hypercellular (M:E 10:1)
* polycythemia - hypercellular (panmyelosis)
* ET - normal cellularity
* primary myelofibrosis - hypercellular → **_hypo_**cellular
* fibrosis
* CML - yes: EMH in accelerated phase
* polycythemia - yes: EMH in spent phase
* ET - _NO_
* primary myelofibrosis - yes: EMH in fibrotic phase
* other features
* CML - psuedo-gaucher cells (sea-blue histiocytes)
* primary myelofibrosis - dilated sinuses in fibrosis
39
which MPNs result in extramedullary hematopoiesis? during which phases?
* CML - EMH in accelerated phase
* polycythemia - EMH in post-polycythemic /spent phase
* primary myelofibrosis - fibrotic phase
40
which MPNs result in organomegally?
* CML - splenomegaly \> hepatomegaly: chronic phase
* polycythemia - splenomegaly \> hepatomegaly: spent phase
* ET - NO ORGANOMEGALLY
* primary myelofibrosis: SEVERE splenomegaly
41
contrast the clinical presentation of each MPN
* ALL can result in vascular abnormalities (thrombocytopenia or thrombocytosis) depending on megakaryocyte function
* ALL EXCEPT primary myelofibrosis: splenomegaly
* CML - anemia sx
* **palor**
* fatigue
* tachycardia / dyspnea
* polycythemia - polycythemia sx:
* **plethora**
* HTN
* HA
* dizziness / paresthesia
42
aspirate from which MPN often shows a “dry tap”?
primary myelofibrosis
43
which MPNs can result in peripheral tear-drop cells?
* polycythemia
* primary myelofibrosis
44
which MPNs can result in peripheral tear-drop cells?
* polycythemia
* primary myelofibrosis
45
