Haematopathology

THE MYELOID NEOPLASMSDr Brian Mitchelson

Qatar Cardiovascular Research Centre

THE MYELOID CELL LINES

The term “myeloid” includes all cells belonging to the granulocyte (i.e., neutrophil, eosinophil, basophil), monocyte/macrophage, erythroid, megakaryocyte, and mast cell lines. Myeloid malignancies are clonal diseases of the hematopoietic stem or progenitor cells.These malignancies can be present in the bone marrow and peripheral blood. They result from genetic and epigenetic alterations that disrupt key haematogenic processes such as self-renewal, proliferation and impaired differentiation.Categorization of the disorders is based on the morphology, cytochemistry, phenotype, genetics, and clinical features of the various myeloid disorders,

MYELOID NEOPLASMS

The World Health Organisation (WHO) categorize these as:

(1)Myelodysplastic Syndromes (MDSs)

(2) Myeloproliferative neoplasms (MPNs)

(3) Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

(4) Myeloid malignancies associated with eosinophilia and abnormalities of growth factor receptors derived from platelets or fibroblasts.

Examples of Myeloid Neoplasms.

1. Acute myeloid leukemia

2. Myelodysplastic syndromes (MDS)

2.1 Refractory cytopenia with unilineage dysplasia Refractory anemia; Refractory neutropenia;

Refractory thrombocytopenia2.2 Refractory anemia with ring sideroblasts2.3 Refractory cytopenia with multilineage dysplasia2.4 Refractory anemia with excess blasts-12.5 Refractory anemia with excess blasts-22.6 Myelodysplastic syndrome with isolated deletion(5q)2.7 Myelodysplastic syndrome, unclassifiable

3. Myeloproliferative neoplasms (MPN) 3.1 Chronic myelogenous leukemia3.2 Polycythemia vera3.3 Essential thrombocythemia3.4 Primary myelofibrosis3.5 Chronic neutrophilic leukemia3.6 Chronic eosinophilic leukemia, not otherwise

categorized3.7 Hypereosinophilic syndrome3.8 Mast cell disease3.9 MPNs, unclassifiable

4. Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

4.1 Chronic myelomonocytic leukemia4.2 Juvenile myelomonocytic leukemia4.3 Atypical chronic myeloid leukemia4.4 MDS/MPN, unclassifiable

5. Myeloid neoplasms associated with eosinophilia and abnormalities of PDGFR-A or -B, or FGFR1

5.1 Myeloid neoplasms associated with PDGFR-A or -B rearrangement5.2 Myeloid neoplasms associated with FGFR1 rearrangement

(8p11 myeloproliferative syndrome)

1. Acute Myeloid Leukemia AML

AML is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age but is a relatively rare disease. The symptoms include fatigue, shortness of breath, easy bruising and bleeding, and an increased risk of infection. Several risk factors and chromosomal abnormalities have been identified, but the specific cause is not clear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.

AML has several subtypes and the treatment and prognosis varies among subtypes.

The five-year survival rates vary from 15–70%, and the relapse rate varies from 33–78%, depending on subtype.

AML is treated initially with chemotherapy aimed at inducing a remission; patients may go on to receive additional chemotherapy or a hematopoietic stem cell transplant.

Recent research into the genetics of AML has resulted in the availability of tests that can predict which drug or drugs may work best for a particular patient, as well as how long that patient is likely to survive.

Bone marrow aspirate of AMLThe arrows show the presence of Auer Rods in the cytoplasm of the blast cells. These azurophilic granular rod structures are only found in AML

A blood film from AMLNote the cell size, large off-centre nucleus and scarce cytoplasm.

A bone marrow trephine biopsy of AML

The biopsy shows presence of large numbers of the abnormal myeloblasts in the bone marrow.

Response to Lenalidomide Therapy in AML

Bone marrow aspirate (hematoxylin and eosin – light microscopy) at the time of diagnosis of leukemic transformation with 34% myeloblasts.

Repeat bone marrow aspirate after 3 months of Lenalidomide now with 5% myeloblasts, improved granulocytic maturation and normal peripheral blood counts.

Genetic Karyotyping of AMLThe arrow shows the deletion of 7q

2. Myelodysplastic Syndromes (MDS)

MDS covers a wide range of neoplasms each with their own characteristic features which we will see in the next slides.

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant hematopoietic stem cell disorders characterized by dysplastic and ineffective blood cell production with a variable risk of transformation to acute leukemia.

These disorders may occur de novo or arise years after exposure to potentially mutagenic therapy (eg, radiation exposure, chemotherapy).

Patients with MDS have a variable reduction in the production of normal red blood cells, platelets, and mature granulocytes. This often results in a variety of systemic consequences including anemia, bleeding, and an increased risk of infection.

MDS occurs most commonly in older adults with a median age at diagnosis in most series of ≥65 years and a male predominance.

Onset of the disease earlier than age 50 is unusual with the exception of treatment-induced MDS but rare cases of MDS have been reported in children at a median age of six years. The risk of developing MDS increases with age. In one study, the annual incidence per 100,000 was estimated to be 0.5, 5.3, 15, 49, and 89 for individuals <50 years of age; 50 to 59; 60 to 69; 70 to 79; and >80 years, respectively

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PATHOLOGIC FEATURES

Myelodysplastic syndrome (MDS) is characterized by abnormal cell morphology (dysplasia) and quantitative changes in one or more of the blood and bone marrow elements (ie, red cells, granulocytes, platelets).

CBC — Complete blood count with leukocyte differential almost always demonstrates a macrocytic or normocytic anemia; neutropenia and thrombocytopenia are more variable.

Pancytopenia (ie, anemia, leukopenia, and thrombocytopenia) is present at the time of diagnosis in up to 50 percent of patients.

While isolated anemia is not uncommon, less than 5 percent of patients present with an isolated neutropenia, thrombocytopenia, or monocytosis in the absence of anemia.

●Anemia – Anemia is almost uniformly present and is generally associated with an inappropriately low reticulocyte response. The mean corpuscular volume (MCV) may be macrocytic (>100 fl) or normal. The red cell distribution width (RDW) is often increased reflecting the presence of increased variability in red cell size, also called anisocytosis. The mean corpuscular haemoglobin concentration (MCHC) is usually normal, reflecting a normal ratio of hemoglobin to cell size.

●Leukopenia – Approximately half of patients have a reduced total white blood cell count, usually resulting from absolute neutropenia. Circulating immature neutrophils (myelocytes, promyelocytes, and myeloblasts) may be identified, but blasts constitute fewer than 20 percent of the differential count.

●Thrombocytopenia – Varying degrees of thrombocytopenia are present in roughly 25 percent of patients with MDS. Unlike anemia, isolated thrombocytopenia is not a common early manifestation of MDS. However, a thrombocytopenic presentation with minimal morphologic dysplasia has been described in patients in whom del(20q) was the sole karyotypic abnormality. Such patients may be easily misdiagnosed as having immune thrombocytopenia (ITP).

●Thrombocytosis – Thrombocytosis is less commonly seen in MDS than thrombocytopenia. In one report, of the 388 patients diagnosed with MDS from 1980 to 2006 at a single institution, 31 (8 percent) presented with a high platelet count. Among these patients, there was a low incidence of spontaneous bleeding or thromboembolic events. Thrombocytosis has been described in 5q- syndrome, 3q21q26 syndrome, and refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T), which is often associated with activating mutations in JAK2.

Myelodysplastic syndromesRefractory anemia with ring sideroblasts

Myelodysplastic syndromesRefractory cytopenia with unilineage dysplasia

Myelodysplastic syndromesMegaloblastic erythroid precursors seen on MDS display an "open" conformation of chromatin

Myelodysplastic syndromesBone marrow biopsy showing cells undergoing karyorrhexis among necrotic marrow cells in a patient with advanced MDS and progressive bone pains.

Myelodysplastic syndromes

Peripheral blood smear showing leukoerythroblastic picture with immature myeloid cells in a patient with myelodysplasia and bone marrow necrosis.

Myelodysplastic syndromesRefractory cytopenia with multilineage dysplasia (RCMD). Bone marrow biopsy (H&E stain). This image illustrates an abnormally small megakaryocyte with hypolobated nucleus. Note the dense, pink-staining cytoplasm

Myelodysplastic syndromesHypolobulated granulocytes are abundant in this marrow from a patient with myelodysplastic syndrome.

Myelodysplastic syndromeMegakaryocyte with multiple abnormal lobes. Some of these are disconnected.

Myelodysplastic syndromeRefractory cytopenia with multilineage dysplasia

3. Myeloproliferative Neoplasms (MPN)

The myeloproliferative neoplasms (MPNs), are characterized by the clonal proliferation of one or more hematopoietic cell lineages, predominantly in the bone marrow, but sometimes in the liver and spleen. In contrast to myelodysplastic syndromes (MDS), MPNs demonstrate terminal myeloid cell expansion into the peripheral blood.

There are six different types of MPN. They are generally distinguished from each other by the type of cell which is most affected. These are:

1.Polycythemia vera - an overproduction of red blood cells

2.Essential thrombocythemia - overproduction of platelets

3. Chronic myelomonocytic leukaemia (CMML) - overproduction of white cells granulocytes)4.Chronic neutrophilic leukaemia - overproduction of neutrophils

5.Chronic eosinophilic leukaemia - overproduction of eosinophils.

6. Idiopathic myelofibrosis - a condition in which bone marrow tissue is gradually replaced by fibrous scar-like tissue, disrupting normal blood cell production

In many cases these diseases develop slowly and get worse gradually. In some cases myeloproliferative neoplasms can progress to leukaemia.

Treatment depends on the type of MPN, the severity, general health and age of the person diagnosed.

Treatment is generally aimed at reducing the excessive number of blood cells in circulation, and at preventing and treating the symptoms and complications of the disease.

Polycythaemia (Rubra) Vera, also known as primary polycythaemia vera, is a disorder where too many red cells are produced in the bone marrow, without any identifiable cause. These cells accumulate in the bone marrow and in the blood stream where they increase the blood volume and cause the blood to become thicker, or more 'viscous' than normal. In many people with polycythaemia vera, too many platelets and white cells are also produced.

Polycythaemia vera is a rare chronic disease diagnosed in an estimated 2 to 3 people per 100,000 population. Although it can occur at any age, polycythaemia vera usually affects older people, with most patients diagnosed over the age of 55 years. Polycythaemia vera is rare in children and young adults. It occurs more commonly in males than in females.

Polycythaemia Vera

Diagnosis

Polycythaemia vera is diagnosed using a combination of laboratory tests and a physical examination.

Full blood countPeople with polycythaemia vera have a high red cell count, haemoglobin level and haematocrit (>52 % in men or >48% in females) due to the excessive production of red cells. The haematocrit is the percentage of the whole blood that is made up of red cells. A raised white cell count (especially a raised neutrophil count) and a raised platelet count are also common findings.

The Red Cell Mass is the total number of red cells circulating in your blood. Polycythaemia vera may be diagnosed when the red cell mass is 25% greater than the average normal expected value. Other findings that help confirm the diagnosis of polycythaemia vera include an enlarged spleen (splenomegaly) and the presence of the JAK2 mutation or other cytogenetic abnormalities in your blood or bone marrow cells.

JAK2 Mutation testingJAK2 mutations (particularly the V617F mutation) can be found in more than 95% of people with Polycythaemia vera. This test can be performed on a blood sample and will help to confirm the diagnosis of a myeloproliferative neoplasm. It doesn't help distinguish polycythaemia vera from essential thrombocythaemia or primary myelofibrosis.

Bone marrow examinationIn polycythaemia vera the bone marrow is often very active with abnormally high numbers of normal cells. Iron stores may be depleted since iron is being used to make more and more red cells

Bone Marrow biopsy –Polycythemia Vera

The bone marrow in polycythemia vera is hypercellular as a result of an increase in myeloid, erythroid, and megakaryocytic elements.

Essential Thrombocythemia (ET)

ET is characterized by a sustained clonal proliferation of megakaryocytes in the bone marrow8, with a peripheral blood platelet count greater than 600 x 109/L. This platelet count threshold has been decreased to greater than 450 x 109/L in the most recent WHO classification. Causes of reactive thrombocytosis must be excluded. The underlying cause of the disease is unknown.

EpidemiologyThe incidence of the disease is approx. 2.5/100,000 population per year and is the lowest among the chronic MPNs.

There may be a higher prevalence in younger women.

The median age at diagnosis is 60 years.

Pathophysiology

The proliferation of megakaryocytes is primarily caused by clonal stem cells, as confirmed by enzyme and genetic analysis.

Megakaryocyte progenitor cells in ET are hypersensitive to the action of several cytokines, including IL-3 and IL-6, and possibly thrombopoietin.

This leads to increased platelet production. There is controversy regarding spontaneous megakaryocyte formation in ET.

The JAK2 mutation is found in 50% to 60% of ET patients.

Patients lacking mutations in JAK2 may instead demonstrate activating mutations of the thrombopoietin receptor, MPL, MPL W515K or MPL W515L.2

Diagnosis

Patients need to fulfill the following criteria:

(1)Platelet count >600 x 109/L; (2)Megakaryocytic hyperplasia on bone marrow aspiration and biopsy, (3)Absence of the Philadelphia chromosome; (4)Absence of infection, inflammation, and other causes for reactive thrombocytosis; (5)Normal red blood cell mass or a haemoglobin concentration <13 g/dL; (6)The presence of stainable iron in a bone marrow aspiration or ≤1 g/dL increase in haemoglobin concentration after a one month trial of oral iron therapy.

ET Blood Film Although some variation in platelet size is present, the platelets are not otherwise atypical but show a significant increase in numbers.

ET Bone Marrow Trephine Biopsy Megakaryocytes in essential thrombocythemia are not only increased in size and number but also have deeply lobulated and hyperlobated nuclei and tend to form small clusters.

Chronic Myelomonocytic Leukaemia (CMML)

Pathophysiology

CMML is a clonal disorder of a bone marrow stem cell line.

Monocytosis is a major defining feature.

CMML exhibits heterogenous clinical, haematological, and morphologic features, varying from predominantly myelodysplastic to predominantly myeloproliferative.

Diagnosis

CMML is characterized pathologically by the following:

1.Persistent monocytosis is greater than 1×109/L in the peripheral blood.2.No Philadelphia chromosome or BCR/ABL fusion gene.

3.Fewer than 20% blasts in the blood or bone marrow.

4. Dysplasia involving one or more myeloid lineages or, if myelodysplasia is absent or minimal, either an acquired clonal cytogenetic bone marrow abnormality or at least 3 months of persistent peripheral blood monocytosis, if all other causes are ruled out.

Bone Marrow Trephine Biopsy CMMLMonocytic elements are increased in this bone marrow aspirate

Blood Film from CMML Monocytosis and the presence of myelocytes, metamyelocytes and promyelocytes is typical of CMML

Chronic Neutrophilic Leukaemia (CNL)

Chronic neutrophilic leukemia (CNL) is a rare chronic myeloproliferative neoplasm of unknown etiology

It is characterized by sustained peripheral blood neutrophilia (>25 × 109/L) and hepatosplenomegaly.

The bone marrow is hypercellular.

No significant dysplasia is found in any of the cell lineages, and bone marrow fibrosis is uncommon.

Diagnosis

Cytogenetic studies are normal in nearly 90% of the patients.

In the remaining patients, clonal karyotypic abnormalities may include +8, +9, del (20q) and del (11q).

There is no Philadelphia chromosome or BCR/ABL fusion gene.

CNL is a slowly progressive disorder, and the survival of patients is variable, ranging from 6 months to more than 20 years.

Bone marrow smear from CNLBone marrow smears show increased granulocytic elements with predominance of segmented neutrophils and bands

Peripheral Blood Film CNLChronic neutrophilic leukemia. The peripheral blood smear shows an absolute neutrophilia without the significant left shift, vacuolization, or toxic granulation usually associated with a reactive process. Döhle bodies (arrows) are often present in the cytoplasm of neutrophils

Chronic Eosinophilic Leukaemia(CEL)

Chronic eosinophilic leukemia is a disease in which too many white blood cells (eosinophils) are produced in the bone marrow.

In chronic eosinophilic leukemia, there are too many eosinophils in the blood, bone marrow, and other tissues.

There is no dysplasia of the eosinophils.

Chronic eosinophilic leukemia may stay the same for many years or it may progress quickly to acute leukemia.

Diagnosis

The main criteria for diagnosing eosinophilic leukemia are:

An eosinophil count in the blood of 1.5 x 109 /L or higher that lasts over time.No parasitic infection, allergic reaction, or other causes of eosinophilia.

In addition to a physical examination, the following tests may be used to diagnose eosinophilic leukemia:

Blood tests. The diagnosis of eosinophilic leukemia begins with a complete blood count (CBC). If the blood contains many eosinophils (see criteria above), eosinophilic leukemia is suspected.

Bone marrow aspiration and biopsy. Many immature cells, blast cells, in the bone marrow are a sign of acute rather than chronic eosinophilic leukemia.

Molecular testingIf an eosinophilia is found, a molecular genetic analysis should be done to test for the mutation FIP1-like platelet-derived growth factor alpha.

Cytogenetics may also be used to determine any abnormality and also to guide a suitable treatment regime.

Chronic Eosinophilic Leukemia Bone marrow biopsy showing eosinophilia

Chronic Eosinophilic Leukemia Peripheral blood film – a significant increase in the number of eosinophils in circulation.

Idiopathic Myelofibrosis MF

Myelofibrosis is a rare condition that affects the bone marrow.

In MF, scar tissue builds up inside the bone marrow and blood cells are not produced properly or in the correct numbers.

It can affect people at any age, including children, but it's most common in people over 50.

MF can occur in people who haven’t any history of problems with their bone marrow. This is called primary myelofibrosis. MF can also develop in people who have essential thrombocythaemia (ET) or polycythaemia vera (PV). This is called post-ET myelofibrosis or post-PV myelofibrosis.

These are all called myelofibrosis as they behave in the same way.

People with MF may have low levels of one or more types of blood cells. If the bone marrow becomes scarred (fibrosed), it may make fewer blood cells. Some people have too few of some types of blood cells and too many of another type.

To make up for fewer blood cells being made in the bone marrow, other parts of the body, usually the spleen and liver, begin to make blood cells. As the spleen begins to make blood cells, it grows in size.

The enlarged spleen may ‘hold on’ to blood cells, instead of releasing them into the blood. The spleen may also destroy blood cells. This can reduce the numbers of blood cells in the blood.

Diagnosis

Tests and investigations that may be done to confirm a diagnosis of MF include:

JAK2 test This blood test checks for a change (mutation) in a gene called JAK2 which helps control how many blood cells are made. A spontaneous mutation in the gene, which happens during the person's lifetime, can cause MF. This is a non-hereditary mutation

CALR blood testBlood tests might also check for a change in another gene called calreticulin (CALR). As with the JAK2 gene change, it happens during the person's lifetime. Again this is non-hereditary.

Bone marrow sample (biopsy and smear)

Idiopathic Myelofibrosis A bone marrow trephine biopsy showing the increased fibrous tissue (stained black) within the bone marrow spaces

Idiopathic Myelofibrosis Bone marrow biopsy showing extensive fibrosis with few germinal cells.

Juvenile Myelomonocytic Leukaemia JMML

Juvenile myelomonocytic leukemia (JMML) is a rare childhood cancer that usually occurs in children younger than 2 years old.

In JMML, too many myelocytes and monocytes (two types of WBCs) are produced from immature blast stem cells.

These myelocytes, monocytes, and blasts overwhelm the normal red and white cell production in the bone marrow and other organs, causing the symptoms of JMML.

Diagnosis

Blood tests. Tests such as a complete blood count, liver and kidney function panels, and blood chemistries can give important information about the number of normal blood cells in the body and how well the organs are functioning. The blood film will also be examined under a microscope to check for abnormal shapes or sizes.

Bone marrow aspiration.This will also be examined microscopically for abnormal cells.

Juvenile myelomonocytic leukemia Note the large numbers of both immature myeloid neutrophils and monocytes.

Juvenile myelomonocytic leukemia Note the bizarre nuclear lobulation of the cell types

Atypical Chronic Myeloid Leukaemia (aCML)

aCML is a chronic myeloproliferative disorder with a clinical and hematological picture similar to chronic myelogenous leukemia (CML) but lacking Philadelphia chromosome and BCR - ABL or PDGFR-B rearrangements.

Atypical CML is characterized by the combination of: 10-20% of immature granulocytes; marked granulocytic dysplasia and both less than 2% of basophils and less than 10% of monocytes.

Diagnosis

Peripheral blood film: This shows a leukocytosis with a high count of immature granulocytes. By definition monocytes are less than 10% and basophils less than 2%. Anemia is more frequent than thrombocytopenia. Bone marrow: Hypercellular with myelodysplastic features of the three series, most marked in granulocytic lineage. Blast cell infiltration ranges from 0% to 10%.

Atypical Chronic Myeloid LeukaemiaMarked granulocytic hyperplasia and dysplasia (convoluted lobulation of nuclei, pseudo-Pelger-Huet forms), <20% blasts

Atypical Chronic Myeloid Leukaemia

Abnormal chromatin clumping. Note neutrophils with abnormal condensation of the nuclear chromatin, which is the hallmark of this condition.

MDS/MPN, unclassifiable

Myelodysplastic/Myeloproliferative Unclassifiable Neoplasm:(MDS/ MPN-UC)This is also known as mixed myeloproliferative/ myelodysplastic syndrome, which does not fit a single criterion but is unclassifiable with overlapping feature of both syndromes.

It shows features of both myeloproliferative disease and myelodysplastic disease but does not meet the criteria for any of the other MDS/MPN entities.

Diagnosis

Diagnostic criteria for MDS/MPN-UC can be either:The combination of four sets of criteria (a–d):

A.Clinical, laboratory, and morphologic features of myelodysplastic syndrome (MDS) (e.g., refractory anemia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, and refractory anemia with excess of blasts) with fewer than 20% blasts in the blood and bone marrow. B.Prominent myeloproliferative features, e.g. platelet count greater than 600 × 109/L associated with megakaryocytic proliferation, or white blood cell count greater than 13.0 × 109/L with or without splenomegaly.

C. No history of an underlying chronic myeloproliferative disorder (CMPD), MDS, or recent cytotoxic or growth factor therapy that could cause the myelodysplastic or myeloproliferative features.

D. No Philadelphia chromosome or BCR/ABL fusion gene, del(5q), t(3;3)(q21;q26), or inv(3)(q21q26). or:

Mixed myeloproliferative and myelodysplastic features that cannot be assigned to any other category of MDS, CMPD, or MDS/MPN.

Atypical Chronic Myeloid LeukaemiaBone Marrow biopsy reveals a hypercellularity (100%) with markedly increased myeloid: erythroid ratio (26:1). Dysplastic megakaryocytes are indicated by arrows.

Atypical Chronic Myeloid Leukaemiamarked leukocytosis with many myeloid precursors :promyelocytes, myelocytes, and metamyelocytes,

Myeloid neoplasms associated with PDGFR-A or -B rearrangement and myeloid neoplasms associated with FGFR1 rearrangement (8p11 myeloproliferative syndrome)

There are three main myeloproliferative and lymphoid neoplasms associated with the rearrangement of the PDGFR-A, PDGFR-B and FGFR-1 genes.

All result from the formation of a fusion gene encoding an aberrant tyrosine kinase.

This disease is associated with PDGFRA rearrangement that is associated with FIP1L1-PDGFRA formed as a result of a cryptic deletion at 4q12.

Presentation is generally as chronic eosinophilic leukemia (CEL) but can be acute myeloid leukemia (AML) as well.

Diagnosis

Definitive Diagnostic Methods:

Bone marrow

FISH ( Fluorescent in-situ hybridisation)

Genetic testing

Immunophenotyping

Myeloid neoplasms associated with PDGFR-A or -B rearrangement and myeloid neoplasms associated with FGFR1 rearrangement

The peripheral blood film showed many morphologic abnormalities of eosinophils, including of size, granulation, and nuclear lobulation.

Myeloid neoplasms associated with PDGFR-A or -B rearrangement and myeloid neoplasms associated with FGFR1 rearrangement

The peripheral blood film showed many morphologic abnormalities of eosinophils, including of size, granulation, and nuclear lobulation.

Myeloid neoplasms associated with PDGFR-A or -B rearrangement and myeloid neoplasms associated with FGFR1 rearrangement

The arrow shows a blast cell in the peripheral blood.

The End of Part 2

Thank you

I would like to thank the following for the use of several images and data:Lichtman’s Atlas of HematologyThe American Society of HematologyWeill Cornel UniversityHematopathology for medical education – WebPathAtlas of Hematopathology | 978-0-12-385183-3 | Elsevier