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S3B5 Pathology > Chronic Myeloproliferative Neoplasms (MPN) + Overview > Flashcards

Chronic Myeloproliferative Neoplasms (MPN) + Overview Flashcards

1
Q

What are the 4 main categories of myeloid neoplasms?

A
  1. Myeloproliferative neoplasms
  2. Myelodysplastic syndromes
  3. Myeloproiferative / myelodysplastic neoplsms
  4. Acute myeloid leukemias
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2
Q

What features are common to all 4 types of myeloid neoplasms?

A

involve blood, bone marrow

loss of normal control of proliferation

suppression normal hematopoietic cells

may all progress to AML

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3
Q

The clinical disease is related to what variables of the myeloid neoplasms?

A

stage of development of neoplastic cells

clinical effects of leukocytosis or cytopenias

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4
Q

What are the general features associated with Myeloproliferative neoplasms (MPN)?

A

increased production one or more types of mature/maturing blood cells

effective hematopoiesis with increases in peripheral blood cell count

no dyspoiesis (abnormal formation of blood cells) - except for megakaryocytes

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5
Q

What are the general features associated with Myelodysplastic syndromes (MDS)?

A

ineffective hematopoiesis → peripheral blood cytopenias

varying degrees dyspoiesis in one or more cells lines

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6
Q

What are the general features associated with Myeloproliferative/myelodysplastic neoplesms (MPN/MDS)?

A

neoplasms with overlapping features of MPN & MDS

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7
Q

What are the general features associated with Acute myeloid leukemias (AML)?

A

accumulation immature myeloid forms in bone marrow

normal hematopoiesis is suppressed → peripheral blood cytopenias

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8
Q

What is the only myeloid neoplasm in which you will not see peripheral blood cytopenia?

A

Myeloproliferative neoplasm (MPN)

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9
Q

What clinical features would you expect to see in a patient with myeloproliferative neoplasm?

A
  • hypercellular bone marrow
  • maturation is present
  • increased myeloid cells in peripheral blood
  • abnormal megakaryocytes with relatively normal granulocytes & erythroid precursors
  • organomegaly (splenomegaly/hepatomegaly)
  • variable transformation to a spent phase
    • marrow fibrosis & peripheral blood cytopenias
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10
Q

What is the molecular abnormalities found in myeloproliferative neoplasms? What are the impacts of this mutation?

A

clonal abnormalities involve genes that encode cytoplasmic or receptor protein tyrosine kinases

  • circumvent normal controls on proliferation
  • lead to growth factor-independent cell proliferation & survival of marrow progenitors
  • differentiation is not impaired - cells will continue to mature
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11
Q

What is the typical clinical outcome associated with chronic myeloproliferative neoplasms?

A

typically indolent

develop over months to years

most people live for many years

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12
Q

What are the 4 classifications for chronic myeloproliferative neoplasms?

A
  • chronic myelogenous leukemia
    • BCR-ABL1 positive
  • Polycythemia vera
  • Primary myelofibrosis
  • Essential thrombocytosis
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13
Q

What genetic abnormality is associated with chronic myelogenous leukemia?

A

BCR-ABL1 fusion gene on the Philadelphia (Ph) chromosome

translocation of ABL1 proto-oncogene on chromosome 9q34 to BCR (breakpoint cluster region) on chromosome 22q11

Ph = abnormal chromosome 22

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14
Q

What is the molecular result of the chimeric BCR-ABL1 gene?

A

usually codes for cytoplasmic fusion protein, BCR-ABL, a constitutively activated tyrosine kinase

this alone is sufficient to cause disease

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15
Q

Is BCR-ABL1 specific to chronic myelogenous leukemia?

A

no- it is required for diagnosis but not entirely specific

it may be seen in some acute leukemias - but fusion transcripts will differ

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16
Q

Chronic myelogenous leukemia is what kind of disorder? It most commonly affects people of what age group?

A

Pluripotent stem cell disorder

middle age (40-60)

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17
Q

What risk factors are associated with chronic myelogenous leukemia?

A

radiation exposure

no inherited predisposition known

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18
Q

What are the three phases of CML?

A

chronic

accelerated

blast

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19
Q

Describe the clinical presentation of chronic phase of CML?

A

insidious onset - malaise, fatigue, weight loss, upper GI discomfort

spleno/hepatomegaly

NO lymphadenopathy

anemia & iron deficiency

bruising & bleeding

hypermetabolic

gout / renal disease

(rarely) visual disturbances

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20
Q

What peripheral blood findings would you expect to see in a patient in the chronic phase of CML?

A

leukocytosis with granulocytic left shift (increased immature myeloid cells)

no significant dyspoiesis

basophilia & eosinophilia

blasts < 2% peripheral blood WBC

normal to increased platelet count

large “buffy” coat

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21
Q

What bone marrow findings would you expect to see in a patient in the chronic phase of CML?

A
  • hypercellular marrow with myeloid hyperplasia
  • increased eosinophils
  • increased megakaryocytes & “dwarf megakaryocytes”
  • no significant dyspoiesis (except megakaryocytes)
  • no increase blasts
  • pseudogaucher cells
    • pump, blue histiocytes
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22
Q

This peripheral blood smear is from what phase of CML?

A

chronic

almost looks like bone marrow, but it is peripheral blood

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23
Q

The provided bone marrow sample is from what phase of CML?

A

chronic

(can’t see, but will be mostly myeloid precursors)

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24
Q

What cells are shown in the provided smear that are characteristic of the chronic phase of CML?

A

dwarf megakaryocytes

(small & hypolobated)

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25
What is the large cell shown in the provided slide that are commonly seen in what myeloid neoplasm? How do these types of cells arise in this condition?
**pseudo-Gaucher cells** chronic phase of CML increased hemophagocytic activity associated with high turnover of hematopoietic cells
26
The provided bone marrow aspirate smear is from what phase of CML?
accelerated (increase in the percent of blasts - still \<20%) may see some dyspoiesis
27
The provided bone marrow biopsy is from what phase of CML?
accelerated (increase in the percent of blasts - still \<20%) may see some dyspoiesis increased # megakaryocytes
28
The provided bone marrow biopsy is from what phase of CML?
blast phase will have \>20% blasts
29
The provided peripheral blood smear is from what phase of CML?
blast phase
30
What features are indicative of the accelerated phase of CML?
* increasing cell counts * (total WBC, basophils & blasts) * increased numbers dwarf megakaryocytes * reticulin fibrosis of the marrow * worsening splenomegaly * **blasts are increased, but \<20% peripheral WBC or bone marrow cells** * worsening thrombocytopenia or thrombocytosis
31
What does a “granulocytic left shift” mean?
increase in immature myeloid cells in peripheral blood
32
What features are indicative of the blast phase of CML?
* **blasts \>20%** of peripheral blood WBC or nucleated cells of marrow * blasts may be myeloid (70-80%) or lymphoid (20-30%) * collections of malignant blasts in other tissues “granulocytic sarcoma”
33
What is the prognosis of CML?
usually fatal within in weeks-months due to infection or bleeding
34
What is the treatment for CML?
* **Tyrosine kinase inhibitors (imatinib**) * highly effective - 5yr survival is 85-90% * hematopoietic stem cell transplant is curative (but w/ many risks)
35
What is polycythemia vera?
MPN with peripheral blood polycythemia & proliferation of _erythroid_, _granulocytic_, and _megakaryocytic_ lineages in marrow
36
What genetic mutation is associated with Polycythemia Vera?
**somatic** gain-of-function mutation **JAK2 V617F** - _low serum erythropoietin level_ cells can proliferate **independent** of growth factors ABSENCE of t(9;22) (**negative BCR-ABL1**)
37
What clinical features are seen in patients with polycythemia vera?
* red face & cyanosis * hypertension, headache, dizziness, paresthesia * GI issues (bleeding) * Gout, weight loss * pruritus * erythromegalia (paroxysmal severe burning pain & throbbing in skin of extremities) * spleno/hepatomegaly * platelets functional * venous / arterial thrombosis * platelets not functional * hemorrhage
38
The clinical features seen in polycythemia vera are mainly due to what physiologic cause?
* increased blood volume * stagnation of blood flow * plethora (red face) and cyanosis
39
What are the three phases of polycythemia vera?
pre-polycythemic phase polycythemic phase (usually diagnosed in this phase) post-polycythemic phase
40
The provided histologic slide is from what phase of polycythemia vera?
polycythemic phase megakaryocytes are _more normally sized_ than with CML red cell morphology is usually normal, but will see an increase Hb & Hct
41
What are the features seen in the pre-polycythemic phase of polycythemic vera?
borderline/mild erythrocytosis difficult to diagnosis - usually asymptomatic
42
What are the features seen in the peripheral blood smear & bone marrow in the polycythemic phase of polycythemia vera?
* Peripheral Blood * increased RBC (normal morphology) * increased hemoglobin * increased hematocrit * mild granulocytosis and/or thrombocytosis * Bone marrow * hypercellular with “panmyelosis” * megakaryocytes are variably hyperlobulated * no dysgranulopoiesis or dyserythropoiesis
43
What does panmyelosis mean?
hyperplasia of all 3 cell lines
44
What are the features seen in the peripheral blood smear & bone marrow in the post-polycythemic phase of polycythemia vera?
* peripheral blood * cytopenia and/or leukoerythroblastosis * many teardrop cells * bone marrow * prominent reticulin and collagen fibrosis * decreased hematopoiesis
45
What are the clinical features seen in the post-polycythemic “spent” phase of polycythemia vera?
extramedullary hematopoiesis (EMH) and splenomegaly
46
What is the prognosis of polycythemia vera & what is the goal of treatment?
incurable with present therapy - may progress to MDS/MPN or AML reduce risk of thrombosis
47
The provided stains are characteristic of what phase of polycythemia vera?
post-polycythemic increased fibrosis (notice cells look like they are all headed in the same direction, this is because of the increased fibrosis)
48
What disease is characterized by **MPN** defined by a **sustained thrombocytosis** (\>450,000) in peripheral blood & **overproduction of megakaryocytes** in marrow with _normal hematocrit._
essential thrombocytosis
49
What are the main sites that are involved with essential thrombocytosis?
blood and bone marrow
50
What genetic mutation is associated with essential thrombocytosis?
NONE are specific for ET **JAK2 V617F** (60%) constitutively active tyrosine kinase → uncontrolled cell expansion _Negative_ BCR-ABL1
51
Describe the typical clinical presentation of a patient with essential thrombocytosis.
* abnormal CBC (w/ thrombocytosis) * normal RBC/Hb/Hct * thombi & bleeding * _No_ spleno/hepatomegaly
52
Why do you not typically see splenomegaly in patients with essential thrombocytosis?
spleen in not a major site of extramedullary hematopoiesis b/c don't see much fibrosis in the BM
53
What peripheral blood morphology would you expect to see in a patient with essential thrombocytosis?
thrombocytosis large & giant platelets (may be larger than red cells) nucleated megakaryocytic fragments Normal RBC & WBC
54
The provided peripheral blood smear is from what Myeloid Neoplasm?
Essential Thrombocytosis increased # platelets & nucleated megakaryocytic fragments
55
What bone marrow findings would you expect to see in a patient with essential thrombocytosis?
normal to slightly hypercellular (blast\<5%) **striking megakaryocytic proliferation with large, hyperlobulated megakaryocytes** other cells have normal morphology _absent/minimal_ reticulin fibrosis
56
The provided bone marrow slide is from a patient with what myeloid neoplasm?
Essential Thrombocytosis striking megakaryocytic proliferation with large, hyperlobulated megakaryocytes
57
What is the prognosis & treatment of essential thrombocytosis (ET)?
small risk of transformation to myelofibrosis or AML low-dose aspirin
58
What are the other names for primary meylofibrosis?
chronic myelofibrosis agnogenic myeloid metaplasia idiopathic myelofibrosis
59
What are the general characteristics associated with primary myelofibrosis?
proliferation marrow megakaryocytes bone marrow fibrosis extramedullary hematopoiesis NO erythrocytosis
60
What is the typical clinical presentation of a patient with primary myelofibrosis?
* **massive splenomegaly** (b/c extramedullary hematopoiesis) * older adults (\>60) * late stage anemia * nonspecific symptoms (fatigue, weight loss, night sweats) * hyperuricemia (gout & stones)
61
What are the molecular/cytogenic abnormalities associated with primary myelofibrosis?
none that are specific **JAK2 V617F** (60%) **CALR** (35%) _Negative_ BCR-ABL1
62
What are the phases of primary myelofibrosis?
pre-fibrotic and fibrotic
63
What is the peripheral blood morphology in the pre-fibrotic phase of primary myelofibrosis?
initially normal progressing to variable thrombocytosis, variable granulocytic leukocytosis no dyspoiesis or left shift anemia w/ normal RBC morphology
64
What is the peripheral blood morphology in the fibrotic phase of primary myelofibrosis?
* moderate normochormatic normocytic anemia with leukoerythroblastosis * marked anisopoikilocytosis (dif size & shape) with teardrop cells * thrombocytopenia with large, bizarre platelets & megakaryocyte fragments
65
What is the bone marrow morphology in the pre-fibrotic phase of primary myelofibrosis?
* hypercellular for age (granulocytic & megakaryocytic hyperplasia) * no dysgranulopoiesis or dyserythropoiesis * megakaryocytes are atypical * absent/minimal fibrosis
66
What is the bone marrow morphology in the fibrotic phase of primary myelofibrosis?
* often a “dry tap” - nothing aspirated * hypocellular marrow with moderate to severe reticulin/collagen fibrosis & dilated sinuses * megakaryocytic atypic * clusters, hyperchromatic bizarre nuclei, cloud-like nuclei
67
What is the major defining feature of CML?
many **neutrophils** & their precursors
68
What is the major defining feature of polycythemia vera?
many of everything especially **erythrocytes** & their precursors
69
What is the major defining feature of essential thrombocytosis?
many platelets and megakaryocytes
70
What is the major defining feature of primary myelofibrosis?
_pre-fibrotic_: thrombocytosis & mild granulocytosis but NO erythrocytosis _fibrotic:_ fibrosis, osteomyelosclerosis & marrow hypoplasia → splenomegaly
71
What steps would you take to work up chronic myeloproliferative neoplasms?
1. CBC & peripheral blood smear 2. bone marry biopsy & aspirate 1. flow cytometry in fibrotic phase 2. staining for CD34, CD117 and/or TdT 3. conventional cytogenetic analysis, FISH, molecular methods 1. looking for specific translocations / markers *\*not tested in this class, but probably good reminder for MEDI*

S3B5 Pathology (13 decks)

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