Summary

Myeloid Neoplasms:

Myeloproliferative neoplasm Myelodysplastic syndromes Acute myeloid leukaemia

-Cell expansion in the peripheral
blood (mature)
-Chronic (less fulminant than
AML)
-Risk of transformation to AML
-On mature cells level
-Peripheral blood cytopenias
-Bone marrow hyperplasia with
abnormal differentiation
-Chronic (less fulminant than
AML)
-Risk of transformation to AML
-On stem cells level
-Same as MDS but with presence
of immature cell in bone marrow
and periphery
-Fulminant
-Results in many immature
(blast) cell

Acute myeloid leukaemia:

-Malignant tumor of myeloid stem cell, characterized by proliferation

and accumulation of very immature cells (myeloblasts).

-Caused by acquired mutations

-May involve different cell lines in myeloid series giving rise to different
types of AML, For example: Involvement of monocytic series ->
monocytic/monoblastic leukemia.

-Classified either by:

FAB: Based on Morphology of blast cells & Cytochemical stains

WHO: Based on molecular defect and biological behavior

-Caused by:

Transformation from another neoplasm disorders, like myeloproliferative

Genetics and syndromes

Some drugs

Environmental: radiation, smoking…

Signs and symptoms:

hemorrhagic findings such as gingival bleeding, ecchymoses, epistaxis, or menorrhagia

(Thrombocytopenia)
Fatigue
Weakness and pallor (Anemia)
Bone pain
Weight loss
Unexplained fever (Neutropenia)
Spleen and liver enlargement

Due to:

1. Suppression of normal Hematopoiesis (marrow failure) -> Pancytopenia

2. Organ infiltration

•Hepatosplenomegaly

• Lymphadenopathy

• Bone pain= Expansion of BM space and infiltration of periosteum

• Involvement of CNS and testes (ALL)

• Gum hypertrophy (acute monocytic leukemia)

Morphology:

Bone marrow:

hypercellular
More than 20% of blasts

**In general, its important to differentiate it from acute lymphoid leukaemia by the differences between
Myeloblasts and lymphoblasts

**Auer rods:
Needle like cytoplasmic
inclusions, formed by fusion of
azurophilic granules
•Stain red purple with Leishman stain or
myeloperoxidase (MPO)
• Only found in AML********

Prognosis:

Mostly proceed with complete remission, but reversible, also:

Myelodysplatic syndrome:

Occurs in men between 50 and 80

Pathogenesis:

• Maturation defects (dyspoiesis) resulting in ineffective hematopoiesis, causing cytopenias (in PB)

• Frequently progress to acute myelogenous leukemia (AML; 30% of cases), also known as
“preleukemia”.

Arises in two different settings:

-Idiopathic or primary MDS: At age > 50

-Therapy related MDS (t-MDS)

• Due to chemotherapy or radiation therapy.

• 2-8 years after treatment

• Higher risk of transformation to acute leukemia.

Patients present with:

• weakness, infections and hemorrhages (all due to cytopenias)

• Typical Profile of a patient with MDS: Elderly person with severe cytopenias, severe anemia and
a constant transfusion requirement.

Laboratory findings

-Peripheral blood:

• Pancytopenia

• RBC: macrocytes with multi nucleus

• WBC: hyposegmented neutrophils (Pseudo Pelger Huet cells) or

Hypersegmented neutrophils, Hypogranulated granulocytes.

• Myeloblasts: less than 20% and may have Auer rods

-Bone marrow:

• Hypercellular.

• Myeloblasts: less than <20% (If >20% disease has progressed to AML).

• Ringed sideroblasts (nucleated RBC with excess iron)

• Megakaryocyte: small, with separated and monolobulated nucleus

Myeloproliferative Neoplasms (MPNs)

• A group of disorders result from unchecked, autonomous proliferation of myeloid cell in the bone
marrow.

• The neoplastic cells and their offspring flood the BM resulting in Erythrocytosis

(↑RBC) , granulocytosis (↑WBC) and thrombocytosis (↑platlets) in the PB.

• one cell line more prominently affected than others.

Two major outcomes:

• bone marrow fibrosis (spent phase).

• transformation into acute leukemia (invariably occurs in CML).

• Classification based on most affected cell line.

Chronic Polycythemia vera Essential Primary

Myelogenous thrombocythemia myelofibrosis
leukemia (CML)
Definition Neoplastic, • Characterized Neoplastic stem Replacement of
proliferation of by Increased cell disorder with marrow by fibrous
pluripotent stem cell
production of proliferation of tissue (collagen)
erythroid megakaryocytes
that is reduce
resulting in:
(mainly), elevated platelet bone marrow
• Extreme increase in granulocytic & count (commonly hematopiesis .

number of megakaryocytic greater than

granulocytes elements.
1,000,000/µL) in Decrease bone
(neutrophils) & its • Increased PB.
marrow
precursors in the BM marrow • Platelets are hematopiesis
& PB.
production is increased; which leads to:
reflected in PB
however, they are 1.cytopenia

• Erythrocytosis nonfunctional. 2.Extramedullary

hematopiesis (liver
and spleen)

Pathogene • t(9;22) = ABL (9) • tyrosine kinase • Genetics: JAK2 Collagen

sis fuses with the break JAK2 mutation mutation (50%), deposition due to
point cluster region in more than MPL or inappropriate
(BCR) on 22.
90% of the Calreticulin release of
• Formation of fusion cases mutation fibrogenic factors (
gene (BCR-ABL)**
released from
• Fusion gene -> neoplastic
tyrosine kinase megakaryocytes
activity -> e.g. TGF beta and
increased mitotic PDGF ). JAK2
activity
mutation is
• Chromosome 22 is present in 50%.

called Philadelphia
chromosome

-Focus on the
percentage of blasts
and progression
Clinical Usually occurs Median age of 60 1. Bleeding
Older patient over
picture between 40 and 60 years
2. Thrombosis
60 years of age.

years of age, and 4 “H”

3. Splenomegaly
• Progressive
onset is slow & • Hyperviscosity: 4. Erythromelalgia anemia • Massive
insidious with increased RBC splenomegaly •
nonspecific mass, which Hyperuricemia
symptoms.
predisposes to and gout.

• Anemia: weakness, thrombotic

fatigue and pallor • episodes (most
Massive common cause
Splenomegaly • of death)
Fullness/ dragging including MI,
sensation in stroke, bowel
abdomen • infarction..)

Hyperuricemia, fever, • Hypervolemia.

weight loss and • Hyperuricemia

sweating. • Splenomegaly.
Laboratory Peripheral Blood:
• Increased • CBC: Peripheral smear:

findings • WBCs: Extreme Hematocrit

Thrombocytosis Leukoerythroblasti
and bone leukocytosis
• >52% in men, (platelets>600,000 c smear

marrow • Granulocytes >48% in cells/uL).

• Presence of
examinatio (Neutrophils) in all women
• Abnormally large Immature WBC
n stages of • Low Plasma platelets.
and nucleated
maturation (left erythropoietin
• Bone marrow: RBCs (nRBCs). •
shift).
Increased number Numerous tear
• Promyelocytes, Peripheral blood of abnormal drop cells
Myelocytes, smear: Packed megakaryocytes (dacryocytes)*

Metamyelocyts, with RBCs with abnormal

band forms & (erythrocytosis)
forms
• WBC findings:

neutrophils.
• Count between
• Myeloblasts <10%.
Bone marrow 10,000 to 50,000 •
• Increased examination: Platelet:

basophils, Early stages: Thrombocytosis

Eosinophils.
Hypercellular with
• RBC: Normocytic All hematopoietic Bone marrow :

to macrocytic elements • Very Early stage:

anemia.
increased (except hypercellular

• Platelets: lymphocytes) • Later on: Bone

Thrombocytosis (Panmyelosis). • marrow fibrosis,
(40-50% of cases).
Late stages: Dry tap common

fibrosis in later • Very late stage:

Bone marrow stages.
fibrotic marrow
examination
may be
• 100% cellular converted to
(normally it is 50% bone
fat).
(osteosclerosis)

• Granulocytes
(neutrophils) in all
stages of maturation

• Increased M/E ratio

• ME ratio = 10:1 to
50:1

• Myeloblasts <10%

• Megakaryocytes
are increased in
number
MDS/MPN (overlapping of myeloproliferative and myelodysplastic)

Hypercellularity of the bone marrow due to proliferation in one or more of the myeloid lineages,
And Increased numbers of circulating cells and/or functionally dysplastic features