Myeloid Neoplasms I Flashcards
what are the four main categories of myeloid neoplasms?
what are the defining characteristics of category?
- 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
neoplasms within which four myeloid neoplasm categories result in cytopenia?
- MDS (MPN / MDS if MDS predominant)
- AML
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
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
neoplasms in each in each myeloid neoplasm category have what in common?
= 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
what are the general features of chronic myeloproliferative neoplasms (MPN)? note:
- pathogenesis
- blood marrow status
- peripheral blood status
- key manifestations
- 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)
list the major types of chronic myeloproliferative neoplasms (MPNs)
- chronic myelogenous leukemia (CML)
- polycthemia vera
- primary myelofibrosis
- essential thrombocytosis (ET)
chronic myelogenous leukemia (CML) - pathogenesis
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
chronic myelogenous leukemia (CML) - comprehensive presentation
= 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
chronic myelogenous leukemia (CML) - chronic phase. how does of the bone, blood and clinical presentation of CML appear during this phase?
= 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 #
chronic myelogenous leukemia (CML) - accelerated phase: how does of the bone, blood and clinical presentation of CML appear during this phase?
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
chronic myelogenous leukemia (CML) - accelerated phase: how does of the bone, blood and clinical presentation of CML appear during this phase?
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
describe the presence of blast cells during each phase of chronic myelogenous leukemia (CML)
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
abnormally large “buffy coat”: layer of leukocytes comprosing the tope of centrifuged peripheral blood
seen in CML: first during the chronic phase
dwarf megakaryocytes: hypo-lobulated nuclei
CML (type of MPN) - first seen in chronic phase.
BM aspirate smear showing blast cells > normal but under 20%
CML (type of MPN) - accelerated phase.
bone marrow with blast cells > normal but under 20%
CML (type of MPN) - accelerated phase.
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
polycythemia vera - pathogenesis
= 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
identify picture, note important features
hypercellular bone marrow + hyper-lobulated megakaryocytes
polycythemia vera (type of MPN) - polycythemic phase
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
identify picture, note important features
peripheral blood smear showing large, hyper-lobulated megakaryocytes + nucleated megkaryocyte fragments
in ET (type of MPN)
bone marrow with LARGE & hyper-lobulated megakaryocytes
in ET (type of PMN)
identify picture, note important features
peripheral blood showing thrombocytopenia with large, bizzare platelets + many tear-drop cells
primary myelofibrosis - fibrotic phase
bone marrow: hypocellular with reticulin/collagen fibrosis & dilated sinuses
primary myelofibrosis - fibrotic phase
bone marrow: hypocellular with reticulin/collagen fibrosis & dilated sinuses
primary myelofibrosis - fibrotic phase
