Myeloid Neoplasms II

Question 1

review the general characteristics of myelodysplastic neoplasms (MDNs)

Answer 1

• hematopoiesis: ineffective
• dyspoesis: in one or more lineages
• blood: peripheral blood cytopenia
• bone marrow: hypercellularity
• manifestations: organomegally uncommon

Question 2

compare and contrast MPNs and MDNs in terms of

• hematopoiesis
• dyspoesis
• blood cellularity
• bone marrow cellularity
• organ presentation

Answer 2

• hematopoiesis
  
  • MPN: effective
  • MDN: ineffective
• dyspoesis
  
  • MPN: in megakaryocytes only
  • MDN: in 1+ lineages
• blood cellularity:
  
  • MPN: increased cell counts (mostly)
  • MDS: cytopenia
• bone marrow: both hypercellular
• organomegally:
  
  • MPN: common
  • MDN: uncommon

Question 3

what are the general clinical components of MDNs?

Answer 3

• common in older adults (median age of 70)
• male predominance
• sx are:
  
  • largely related to cytopenia
  • generally includes anemia - to a degree that most MDN pts require blood transfusions

Question 4

what are Aeur rods? in what situations are they seen?

Answer 4

• rod shaped structures that are = fused lysosomes / primary neutrophilic granules
• see in:
  
  • RAEB-2 (MDN)
  • acute myeloid leukemias (MPN/MDN)

Question 5

identify this picture, note important features

Answer 5

• Aeur rods: fused lysosomes / primary neutrophilic granules
• seen in
  
  • RAEB-2 (MDN)
  • acute myeloid leukemias (MPN/MDN)

Question 6

Answer 6

dysgranulopoiesis

Question 7

Answer 7

hypo-granular platelets

dysgranulopoiesis

Question 8

Answer 8

dysmegakaryopoiesis

dysgranulopoiesis

Question 9

list the all the MDN neoplasms

Answer 9

• refractory cytopenia with unilineage dysplasia (RCUD) - anemia, neutropenia, thrombocytopenia
• refractory cytopenia with multilineage dysplasia (RCMD)
• refractory anemia with ring sideroblasts (RARS)
• refractory anemia with excess blasts: RAEB-1, RAEB-2
• myelodysplastic syndrome, unclassified (MDS-U)
• MDS associated with isolated del(5q)

Question 10

describe the bone / blood of RCUD.

note blast / sideroblasts status

Answer 10

refractory cytopenia with unilineage dysplasia

• bone & blood: unilineage dysplasia
  
  • RA - anemia
  • RN - neutropenia
  • RT - thrombocytopenia
• blood: cytopenia
• blasts & ring sideroblasts - within normal range

Question 11

describe the blood / bone of RMCD

note blast / sideroblasts status

Answer 11

= refractory cytopenia with multilineage dysplasia

• blood & bone - multilineage dysplasia
• blood
  
  • cytopenia
  • no blasts
• bone
  
  • < 5% blasts
  • < 15% sideroblasts

Question 12

describe the bone / blood of RARS.

note blast / sideroblasts status

Answer 12

refractory anemias with ringed sideroblasts

• blood
  
  • anemia, often with dimorphic pattern - (two populations of red cells)
  • no blasts
• bone marrow
  
  • < 5% blasts
  • erythroid dysplasia (unilinear)
  • > 15% of erythroid precursors are ringed sideroblasts

Question 13

describe the bone / blood of MDS associated with RAEB-1

note blast / sideroblasts status

Answer 13

refractory anemia with excess blasts-1 (RAEB-1)

• blood
  
  • cytopenia
  • < 5 blasts
• bone
  
  • unilineage / multilineage dysplasia
  • 5-9% blasts

Question 14

describe the bone / blood of MDS associated with RAEB-2

note blast / sideroblasts status

Answer 14

refractory anemia with excess blasts-1 (RAEB-2) = aka preleukemia

• blood
  
  • cytopenia
  • 5-19% blasts
  • +/- Auer rods
• bone
  
  • unilineage / multilineage dysplasia
  • 10-19% blasts
  • +/- Auer rods
  • myeloid maturation arrested

Question 15

compare the blood & bone characteristics of RAEB 1 & RAEB 2 in terms of

• blasts / sideroblasts
• auer rods
• dysplasia
• cell levels
• other features

Answer 15

both MDN

Question 16

describe the bone / blood of MDS associated with isolated del(5q)

note blast / sideroblasts status

Answer 16

• blood
  
  • anemia that is often severe & transfusion-dependent
  • normal or inc platelets
  • blasts < 1%
• bone
  
  • dysplasia in 2+ lineages
  • blasts < 5%
  • ringed sideroblasts < 15%

Question 17

MDS associated del(5q)

• pathogenesis
• demographics
• prognosis

Answer 17

• pathogenesis: deletion of bands 31-33 of the long arm of chromosome 5
• demographics: elderly women
• prognosis: good

Question 18

identify picture, note important features

Answer 18

= RARS (MDN)

• bone marrow (blue = inc iron):
  
  • > 15% erythroid precursors = ringed sideroblasts
  • erythroid dysplasia

Question 19

in which MDN is myeloid maturation arrested?

Answer 19

RAEB-2

Question 20

in which MPNs are ringed sideroblasts present?

Answer 20

• RCUD: < 15%
• RCMD: +/- 15%
• RARS: .>/= 15%

(all in bone marrow)

Question 21

characterized MPN/MDN disorders based on

• peripheral blood counts
• bone marrow cellularity
• hematopoiesis efficacy
• dyspoiesis
• blasts cell presence
• presence of organomegally

Answer 21

• peripheral blood counts - variable
• bone marrow - hypercellular
• hematopoiesis effectiveness - varies, usually less
• dyspoesis - present
• blasts cell - either normal or increased, but always < 20%
• organomegally - common

Question 22

discuss the genetics of MDS/MPN combination disorders

Answer 22

• no specific abnormalities
• are all NEGATIVE for BCR-ABL1

Question 23

which neoplasms are MPN/MDN disorders?

Answer 23

• chronic myelomonocyte leukemia (CMML)

Question 24

chronic myelomonocytic leukemia (CMML) - clinical: pathogenesis, demographics, risk factors

Answer 24

• pathogenesis: no specific genetic linkage
  
  • no Ph chromosome or BCR-ABL2 fusion gene (like in CML)
  • no rearrangement of:
    
    • PDGFRA or PDGRFAB
    • FGFR1
    • PMC1-JAK2
• demographics: older people
• risk factors:
  
  • environmental toxins
  • radiation
  • previous chemo therapy

Question 25

chronic myelomonocytic leukemia (CMML) - morphology in * blood * bone marrow

Answer 25

* blood * **absolute monocytosis** * +/- increase / decrease in * inc: granulocytosis (+/-) * dec: thrombocytopenia, anemia (+/) * dysplasia present - _esp granulocytes_ * bone marrow - nothing specific

Question 26

chronic myelomonocytic leukemia (CMML) - presentation

Answer 26

**just like CML (MPN) except:** like CML, except also includes presence of: * **_tissue based leukemic infiltrates_** * **hepatomegaly common** CML presentation: * **malaise / fatigue** * **pallor (anemia)** * _hyper-metabolic syndrome_ (cancer triad) * weight loss / anorexia * night sweats * fever * **splenomegaly** * gout

Question 27

compare & contrast the blood findings of CML vs CMML

Answer 27

* CML * cellular #s: * increase * **_granulocytosis_ (invariably, basophils)** * **+/- thrombocytosis** * decrease : erythrocytopenia (suppression) * NO MONOCYTE ABNORMALITIES * dyspoesis: * **megakaryocytes- hypo lobulated “dwarf” megakaryocytes** * CMML * cellular #s * increase: * **MONOCYTOSIS** * +/- granulocytes * decrease * +/- erythrocytopenia (suppression) * +/- thrombocytopenia * dyspoesis: * **in granulocytes**

Question 28

what is necessary to make a dx of CMML?

Answer 28

* **persistent blood monocytosis: \> 1x 10³/uL** * **\< 20% blasts in blood or bone marrow** * **genetic requirements:** * _no Ph or BRC-AB1L fusion_ * _no rearrangement of_ * PDGFRA or PDGFRA * FGFR1 * PCM1-JAK2 * leukocytosis common

Question 29

acute myeloid leukemia (AML) - clinical: pathogenesis, demographics, risk factors

Answer 29

* pathogenesis * known risk factors: * radiation * conditions - downs, fanconi anemia * if no known conditions: related to mutations in chromosomes 5 & 7 & arise in the setting of: * **myelodysplasia** * **DNA damaging drugs**: * topoisomerase inhibitors * alkylating agents * demographics * in adults - 80% of leukemias * in children - 20% of leukemias * in neonates - most frequent leukemia

Question 30

discuss the prevalence of AML in * adults * children * neonates

Answer 30

* adults - 80% of acute leukemias * children - 20% of acute leukemias * neonates - most common acute leukemia

Question 31

AML - overall presentation

Answer 31

* a lot like CML * pallor * fatigue * fever * **except** * **organomegally uncommon** * and, lineage specific presentation: * **DIC:** in acute promyelocytic * **gingival hyperplasia;** in monocytic lineage

Question 32

discuss the bone / blood of AML

Answer 32

* blood - anemia, thrombocytopenia like CMML * bone * hypercellular * **blasts \> 20% UNLESS** associated with specific cytogenic abnormalities * myeloblast * monoblasts