Classification of Myeloid Neoplasms: A Comparative Review

Vet Clin Pathol. September 2005;34(3):189-212. 265 Refs

Patricia M McManus

I.                    Introduction

a.       The 30% blast threshold for diagnosing AML was originally advocated by FAB-NCI because it was estimated to be the point at which a myeloid neoplasm becomes sensitive to cytoreductive therapy

b.      In some leukemias, cytogenetic mutations were determined to be better prognostic indicators than either leukemia phenotype or blast percentage, so a classification system that incorporated genetic status was needed

II.                 Human myeloid neoplasms

a.       Much of the old terminology is retained, although new and more precise definitions of those terms are applied

b.      Myelodysplasia is a misnomer for clonal disorders that are more accurately classified as chronic myeloneoplasms

c.       WHO recommends that the diagnostic work-up of patients with suspected myeloid neoplasms always include:

                                                               i.      200-cell differential counts on peripheral blood

                                                             ii.      500-cell differential counts on bone marrow aspirate

                                                            iii.      A bone marrow biopsy

                                                           iv.      Genetic analysis

                                                             v.      A panel of histochemical/cytochemical stains and immunophenotypic markers

d.      Historically, lymphocytes, plasma cells, mast cells and macrophages were excluded from all nucleated cell (ANC) counts

e.       Blasts include myeloblasts, monoblasts, promonocytes, atypical promyelocytes and megakaryoblasts

f.        Erythroblasts are only included in the blast count if the patient has “pure erythroleukemia” with >80% erythroid elements in marrow

g.       WHO recommends that morphologic atypia should be evident in ≥10% of cells within a single lineage to warrant designation as “significant lineage dysplasia” for MDS diagnosis and in ≥50% of cells within 2 or more lineages for “AML with multilineage dysplasia”

h.       Examination of ≥20% megakaryocytes/marrow is recommended when determining the absence or presence of dysmegakaryocytopoiesis

i.         Most emphasis being placed on the presence of micromegakaryocytes as indicators of clonality

j.        Atypical morphologies used as indicators of clonality and not likely subject to interobserver variability include ring sideroblasts and pseudo-Pelger-Huet anomaly

k.      Acute Myeloid Leukemia

                                                               i.      AML accounts for 90% of acute leukemias seen in older patients

                                                             ii.      The marrow blast threshold has been lowered from 30% to 20%

                                                            iii.      The biologic behavior of dysplastic marrow containing between 20% and 30% blasts was determined to be just as aggressive as AML with multilineage dysplasia, suggesting that these 2 diseases should be treated as a single disease

                                                           iv.      Cytogenetics is now recognized as the greatest predictor of survival potential

                                                             v.      Risk groups

1.      Favorable (25% relapse, 70% survival to 4 years)

2.      Intermediate (50% relapse, 40-50% survival to 4 years)

3.      High (70% relapse, 20% survival to 4 years)

                                                           vi.      De novo AML is not usually associated with dysplastic morphologies, frequently has a single low risk cytogenetic defect, has no age predisposition, and is more responsive to chemotherapy

                                                          vii.      AML with dysplasia and AML-therapy-related are more likely to have evolved over time, have multiple, inconsistent, high-risk cytogenetic defects, and are usually seen in older patients

                                                        viii.      Stratification according to:

1.      Presence of recurrent, specific cytogenetic abnormalities

2.      Associated dysplasia

3.      Previous chemotherapy

                                                           ix.      AML with recurrent genetic abnormalities

1.      20-30% of all myeloid leukemias

2.      Most genetic alterations in this group are balanced chromosomal transformations

3.      Acute promyelocytic leukemia

a.       Addressed therapeutically by induction of terminal differentiation using vitamin A-derived trans-retinoic acid

b.      T-RA has fewer dire side effects compared with more conventional chemotherapy

c.       APL is the most common of the AMLs, accounting for ~5-8%, and is the most curable of all AML subtypes, because patients with APL have a 70-80% survival rate at 5 years

d.      APL is characterized by promyelocytes

                                                                                                                                       i.      Variably sized cells with variably shaped, frequently reniform or bilobed nuclei and pleomorphic nucleoli

e.       The hypergranular form is more common

                                                             x.      AML with multilineage dysplasia

1.      Subdivided in 2 groups:

a.       Those patients in which MDS was previously diagnosed

b.      Those in which it was not

2.      Dysplastic morphologies must be evident in at least 2 myeloid cell lines and in 50% of the cells

3.      AML with dysplasia is generally a disease seen in the elderly rather than in children

4.      AML occurring in patients who first presented with MDS is considered a secondary AML

a.       Secondary AML accounts for ≥10% to possibly 40% of all AMLs

                                                           xi.      Therapy-related AML

1.      Subdivided according to agents

a.       Alkylating and/or radiation

b.      Topoisomerase II inhibitor

2.      Risk increases as total dose and age of the patient increases and by specific type of drug

3.      It should be noted that patients treated for a primary neoplasm are already at increased risk of developing second and even third neoplasms because of an increased susceptibility to cancer independent of therapy-associated risks

4.      ALK/RAD t-MDS and ALK/RAD t-AML are classified together, presumably because:

a.       Prognoses are equally poor for both

b.      Neither responds to chemotherapy

c.       Marrow blasts in ALK/RAD t-AML patients are >20% but still a minority cell type

5.      Those that present with t-MDS die without progression to t-AML

6.      ALK/RAD patients, overt disease generally develops after therapy, whereas with Topo II inhibitors, latency to AML is shorter at 203 years

7.      Topo II inhibitor-associated AMLs usually have a very strong monocytic component and show a conventional response to antileukemic therapy predicable by their genetics

                                                          xii.      AML, not otherwise categorized

1.      Most closely reflect the previous French-American-British system

2.      Alpha numeric designations have been discontinued

3.      These leukemias are grouped by what they lack rather than what they have:

a.       Multilineage dysplasia is not apparent

b.      There is no consistent cytogenetic abnormality

c.       There is no history of previous chemotherapy

4.      Acute myeloblastic leukemia without maturation

a.       Generally associated with:

                                                                                                                                       i.      Severe anemia

                                                                                                                                     ii.      Neutropenia

                                                                                                                                    iii.      Thrombocytopenia

                                                                                                                                   iv.      Significant leukocytosis consisting of mostly blasts

b.      Blasts generally are easily identifiable as myeloblasts because of the presence of fine cytoplasmic granules

c.       Blasts constitute most cells within the marrow

d.      Blasts are ≥3% myeloperoxidase (MPO) and Sudan Black B (SBB) positive

5.      Acute myeloblastic leukemia with maturation

a.       ≥10% of cells have evidence of neutrophilic differentiation beyond the myeloblast stage

b.      Myeloblasts must be ≥20% of ANC

6.      Acute myeloblastic leukemia, minimally differentiated

a.       Blasts are negative or <3% positive for cytochemistries

b.      Blasts tend to be:

                                                                                                                                       i.      Medium-sized with finely dispersed to condensed chromatin

                                                                                                                                     ii.      Round or Slightly indented nuclei

                                                                                                                                    iii.      1-2 variably distinct nucleoli

                                                                                                                                   iv.      Agranular variably blue cytoplasm

c.       Blasts constitute most cells within the marrow

7.      Acute myelomonocytic leukemia

a.       Has evidence of maturation in both granulocytic and monocytic lineages

b.      Myeloblasts, monoblasts and promonocytes collectively must be ≥20% of ANC

c.       Neutrophils and neutrophilic precursors and monocytes and monocytic precursors must each account for ≥20% of ANC

d.      Blasts should be ≥30% MPO positive

8.      Acute monoblastic leukemia and acute monocytic leukemia

a.       Contain ≥80% monocytic cells in the marrow with at least 20% monoblasts and promonocytes

b.      If the majority (>50%) of marrow monocytic cells are monoblasts, the diagnosis is acute monoblastic leukemia

c.       If promonocytes are the majority, the diagnosis is acute monocytic leukemia

d.      Frequency associated with:

                                                                                                                                       i.      Hyperleukocytosis

                                                                                                                                     ii.      DIC

                                                                                                                                    iii.      Extramedullary solid tumors in the skin, oral cavity, and CNS

e.       A recent study using current treatment modalities could not establish a significant difference between monocytic AML and nonmonocytic AML in complete remission rates, survival without recurrence, or overall long term survival

9.      AML with predominantly erythroid phenotypes

a.       The first FAB proposal made a diagnosis of erythroleukemia nearly impossible

b.      Synonyms for M6-b include: acute erythremic myelosis, Di Guglielmo’s disease, and in the veterinary literature M6Er

c.       Synonyms for cases with significant nonerythroid components are M6a and Di Guglielmo’s syndrome

d.      The blast threshold has been lowered to 20%

e.       Most cells in these cases are proerythroblasts (rubriblasts)

f.        M6a is now called acute erythroleukemia or acute erythroid/myeloid leukemia

g.       M6b is called pure erythroid leukemia

h.       Primary signs are the result of anemia

i.         As many as 50% of erythroid/myeloid leukemias and erythroleukemias diagnosed in human medicine are therapy related

j.        Have uniformly poor prognoses

10.  Acute megakaryoblastic leukemia

a.       Blast population consisting of ≥50% blast of megakaryocytic lineage

b.      Formerly AML-M7

c.       The blast population ranges from mostly minimally differentiated cells that require immunophenotyping for lineage identification to megakaryoblasts with obvious, albeit abnormal, megakaryocytic traits

d.      Marrows are severely fibrotic

e.       Marrow aspiration may result in a “dry tap”

f.        Present with cytopenias, including thrombocytopenis, although thrombocytosis is possible with AMegL

g.       Fulminant diseases with poor prognoses

11.  Acute leukemias of ambiguous lineage

a.       Those that have 2 distinct blast populations, one myeloid and one lymphoid (bilineal acute leukemias), lack markers for either myeloid or lymphoid lineages, or have blasts that coexpress myeloid and lymphoid markers

l.         Chronic myeloproliferative diseases

                                                               i.      Rare chronic productive neoplasms characterized by peripheral blood increases in mature nondysplatic cells of myeloid lineage, including granulocytes, platelets, and erythrocytes

                                                             ii.      MPD blast cell counts must be <20%

                                                            iii.      Liver and spleen are generally enlarged because of sequestration of cells within these organs or extramedullary hematopoiesis

                                                           iv.      Hypercellular marrows seen early in these diseases are virtually identical to reactive hyperplasias, which are primary differentials to consider during diagnostic evaluation

                                                             v.      Mild to moderate anemia frequently accompanies all these diseases

                                                           vi.      The final event is marrow failure, either as a result of clonal evolution to an acute blastic crisis or sever myelofibrosis

                                                          vii.      The molecular basis for leukemogenesis in these diseases is poorly understood

                                                        viii.      Chronic myelogenous leukemia

1.      Most common and most thoroughly documented MPD is CML

2.      Diagnosis requires detection of either the Philadelphia chromosome or the BCR-ABL fusion gene

3.      The early phenotype is an unexplained, often asymptomatic, markedly elevated neutrophil count

4.      Neutrophilia is not an isolated finding because it is always accompanied by basophilia and, frequently, eosinophilia

5.      Examination of a marrow biopsy indicates a hypercellular state with increased granulopoiesis of all 3 cell types

6.      Atypical megakaryocytes are usually 80% smaller in both cellular and nuclear size compared with normal

7.      Dysgranulopoiesis is not a distinctive feature of CML

8.      Scoring is based on a patient’s age, spleen size, and blast cell, eosinophil, basophil, and platelet counts to determine placement in 3 risk groups – low, intermediate, and high – that predict survival to 96, 65, or 42 months

9.      Today’s treatment regimens include recently approved Imatinib

                                                           ix.      Chronic neutrophilic leukemia

1.      A rare disorder that is diagnosed by exclusion

2.      Virtually identical to a leukemoid response in that it is characterized by leukocytosis of only neutrophilic granulocytes

3.      Circulating neutrophils are variably toxic and mostly mature, with a left shift largely limited to band forms

4.      Extramedullary neutrophilic granulopoiesis is present in the spleen and can be present in the liver

5.      Clonal proliferation of neutrophils that are resistant to apoptosis, resulting in an accumulation of mature cells

6.      Differential diagnosis includes other MPDs with a concurrent neutrophilic component, infection, inflammatory disease, and paraneoplastic response to malignant Neoplasia

7.      In human medicine, a common cause for paraneoplastic Neutrophilia is multiple myeloma

                                                             x.      Chronic eosinophilic leukemia

1.      A clonal proliferation of eosinophils in which internal organs are infiltrated with eosinophils, and there is persistent unexplained eosinophilia for >6 months at >1500 cells/μL

2.      Clinical signs are similar for CEL and HES, and both occur in men far more frequently than women

3.      Morphologically, the only clue useful indistinguishing the two is an increase in blast cells in CEL

4.      Both disorders are multisystemic diseases with infiltrates detected in multiple organs

5.      Cytokine release by eosinophils results in damage to involved organs

6.      Overall survival is good but variable

                                                           xi.      Polycythemia vera

1.      Characterized by clonal erythropoiesis that is independent of normal control process, an elevation of hemoglobin concentration >25% above the reference interval mean, and associated vascular disturbances

2.      The mutation is within the multipotential stem cell

3.      Panmyelosis is a common finding

4.      Peripheral blood neutrophilia, basophilia, and thrombocytosis are common, and marrow megakaryocytic hyperplasia is striking

5.      Two phases in PV progression

a.       The proliferative or “polycythemic phase”

                                                                                                                                       i.      Marrow is frequently hypercellular and organ enlargement is primarily reflective of congestion

b.      Followed by the spent or “postpolycythemic phase”

                                                                                                                                       i.      Typified by cytopenias

                                                                                                                                     ii.      Severe marrow fibrosis

                                                                                                                                    iii.      Splenomegaly secondary to prominent extramedullary hematopoiesis

                                                                                                                                   iv.      Erythrocytes have dacryocyte poikilocytosis

6.      Repeated phlebotomy remains the most typical treatment regimen

7.      Most patients die from thrombotic complications or hemorrhage

                                                          xii.      Chronic idiopathic myelofibrosis

1.      Monoclonal proliferative disease of a multilineage stem cell, manifesting heightened granulopoiesis and megakaryocytopoiesis, massive splenomegaly, and severe reactive marrow fibrosis

2.      Proliferation of fibroblasts is likely influenced by neoplastic hematopoietic cells

3.      Disease is stage as either prefibrotic, which is when 20-30% of patients are first seen, or postfibrotic, which is the more common presentation, but development of fibrosis is progressive rather than abrupt

4.      As marrow fibrosis worsens, a leukoerythroblastic peripheral blood profile develops, and erythrocytes display dacryocyte poikilocytosis

5.      A biopsy generally indicates:

a.       Decreased cellularity

b.      Increased reticulin and collagen fibers

c.       Increased adipocytes

d.      Osteosclerosis

e.       Prominent atypical megakaryocytic proliferation

6.      Death is usually tied to marrow failure

                                                        xiii.      Essential thrombocythemia

1.      Involves primarily the megakaryocytic lineage

2.      Thrombocytosis is common (>600,000 cells/µL) and marrow megakaryocytes are increased, but there is no marrow fibrosis, extramedullary hematopoiesis is minimal, and megakaryocyte atypia is limited to an increase in cell size

3.      Disease is often detected when a CBC is requested for unrelated reasons

4.      Signs, when present, usually reflect vascular occlusion or GI hemorrhage

5.      Diagnosis is often one of exclusion

6.      Treatment of ET is not always needed

                                                        xiv.      Chronic myeloproliferative disease, unclassified

1.      Reserved for cases that do not fit the WHO criteria for any other category or that have features that overlap 2 disorders

m.     Myelodysplastic syndromes

                                                               i.      Characterized by cytopenias secondary to ineffective, and usually morphologically atypical, hematopoiesis, and also are termed dysplastic hematopoiesis or dyshematopoiesis

                                                             ii.      Fairly common in people >70 years old

                                                            iii.      Associated with significant morbidity and a high risk of progression to acute myeloid leukemia

                                                           iv.      The classification system recognizes that some MDS are unclassifiable

                                                             v.      Of importance is recognition of the difficulty in distinguishing between MDS and transient, nonclonal, dysplastic morphologies secondary to other processes, e.g., nutritional deficiencies, toxins, or drug exposure

                                                           vi.      A biopsy is considered an important tool in the diagnosis of MDS

                                                          vii.      Histologic detection of abnormal localization of immature precursors (ALIP) is considered a critical determinant of a poor prognosis

1.      ALIP refers to detection of cluster of immature myeloid cells, e.g., ≥5-8 myeloblasts and promyelocytes in central regions rather than in their typical location, i.e., adjacent to sinusoid walls and end steal surfaces

n.       Myelodysplastic syndromes/myeloproliferative diseases

                                                               i.      MDS are thought to be proliferative disease characterized by heightened apoptosis so that hematopoiesis is ineffective, and the syndromes result in cytopenias

                                                             ii.      Chronic MPDs are thought to be effective proliferations of cells that have heightened sensitivity to growth factors and/or have feedback loop failures, resulting in high peripheral blood counts

                                                            iii.      Some lineages, usually granulocytic and/or monocytic, are effectively proliferative, whereas others, usually erythroid and megakaryocytic, are ineffectively proliferative

                                                           iv.      Patients eventually die from evolution to AML or complications secondary to severe anemia and/or thrombocytopenia

                                                             v.      Chronic myelomonocytic leukemia (CMML)

1.      Patients with proliferative CMML have more pronounced splenomegaly and higher peripheral WBC counts, but other peripheral blood counts, age at diagnosis, marrow blast counts, and survival times are virtually identical to dysplastic CMML

2.      Better predictors of short survival are immature myeloid cells in circulation, >10% blasts in marrow, anemia, lymphocytosis >2500 cells/µL, and thrombocytopenia

3.      Subgrouping is now based on blast percentages in the blood or marrow or the presence of Auer rods

4.      CMML-1 has <5% blasts in the blood and <10% in the marrow

5.      CMML-2 has 5-19% blasts in peripheral blood or 10-19% blasts in marrow or Auer rods

6.      Diagnosis of CMML requires an unexplained monocytosis of >1000 monocytes/µL and dysplasia of one or more myeloid lineages

7.      If dysplasia is minimal or absent, CMML is diagnosed based on the persistence of monocytosis for >3 months or detection of a clonal cytogenetic abnormality within the marrow cells

8.      CML is easiest to identify distinctly because it:

a.       Is defined by its genetics

b.      Has the least granulocytic dysplasia

c.       Has the lowest percentage of monocytes

d.      Has the highest frequency of basophils

9.      CMML is distinguished from CML and aCML by its monocytosis, less pronounced granulocytic left-shifting in the peripheral blood, and higher percentage of erythroid cells in marrow

                                                           vi.      Atypical chronic myeloid leukemia (aCML)

1.      Characterized by significantly dysplastic and left-shifted granulopoiesis

2.      Atypical traits include:

a.       Acquired Pelger-Huet anomaly

b.      Atypical nuclear segmentation

c.       Atypical chromatin clumping

d.      Abnormal cytoplasmic granularity

3.      Leukocyte counts may exceed 300 x 10³ cells/µL

4.      Erythroid dysplasia may manifest as elliptical macrocytes

                                                          vii.      Juvenile myelomonocytic leukemia (JMML)

1.      Rare disease

2.      Pronounced splenomegaly because of increased extramedullary hematopoiesis

3.      Anemia with circulating nRBC

4.      Thrombocytopenia

5.      >10% fetal hemoglobin

6.      Diagnostic criteria include monocytes of >1000 cells/µL in peripheral blood and <20% blasts in blood or marrow

7.      Prognosis is poor

III.               Myeloid neoplasms in animals

a.       Acute myeloid leukemia

                                                               i.      APL in dogs, cats, horses, cattle, or sheep has yet to be reported

                                                             ii.      The lack of animal cases, perhaps, reflects chromosomal differences in location of PML and RARα loci in animals so that breakage and translocation in a similar manner cannot occur readily

                                                            iii.      In all but AML with erythroid phenotype, blast cells should be enumerated relative to ANC, with ANC defined as excluding plasma cells, lymphocytes, mast cells, and macrophages

                                                           iv.      An MDS-Meg diagnosis has never been applied in animals or people

                                                             v.      ALSG recommended a blast threshold of ≥30% in marrow and/or blood, similar to NCI guidelines, but assessment of blood for blast percentages is often left out of published guidelines

                                                           vi.      The inclusion of a diagnosis based on the percentage of blast cells in blood was meant to clarify occasional cased in which the percentage of blast cells in marrow is high but still<30%, whereas the blood blast percentage is ≥30%

                                                          vii.      The most common types of acute leukemia were myeloblastic forms M1 and M2

                                                        viii.      Erythroid leukemias accounted for 20%, with 21 cases of M6 and 10 of M6Er

                                                           ix.      Least common were AUL, AMML, and acute monocytic and acute megakaryoblastic leukemia

                                                             x.      Dyserythropoiesis was significant in M6 and M6Er patients

                                                           xi.      The highest marrow blast cell percentage of ANC were in AUL, AML-M1, and AML5a, whereas the lowest were in AML-M6Er

                                                          xii.      High peripheral WBC counts did not predict high peripheral blast counts

1.      Although cats with monocytic leukemias had the highest leukocyte counts, they were least likely to have circulating blasts because two thirds were noted to be aleukemic

                                                        xiii.      80% of the cats required bone marrow evaluation to confirm the diagnosis

                                                        xiv.      Anemia was noted in 91.3% of the cats

                                                         xv.      Thrombocytopenia was noted in 51.2% of the cats with known platelet counts

                                                        xvi.      Most studies of AML in animals report that splenic involvement is common

                                                      xvii.      Anemia and thrombocytopenia are common

                                                     xviii.      The course of the disease is short, usually only days to weeks

                                                        xix.      The majority of feline AML patients are positive for FeLV

                                                         xx.      The majority of canine patients are large-breed dogs

                                                        xxi.      Most animals are in their early to middle years

b.      Chronic myeloid neoplasms

                                                               i.      MDS is the result of a mutagenic event in the multipotential stem cell

                                                             ii.      Has been shown to be monoclonal in the majority of feline patients and, therefore, is neoplastic

                                                            iii.      Is not reversible and is nonresponsive to chemotherapy

                                                           iv.      Patients can survive for several months and, occasionally, several years with supportive care

                                                             v.      In cats, MDS is strongly associated with FeLV infection

                                                           vi.      MDS is defined by marrow blast cells that may be increased, but are <30% of ANC in marrow with <50% erythroid precursors

1.      Peripheral blood blasts are also <30%

                                                          vii.      Düsseldorf scoring was a better prognostic index than MDS classification

                                                        viii.      Blast percentages for most feline MDS patients reported in the literature are <20%

                                                           ix.      Idiopathic hypereosinophilic syndrome and CEL are difficult to distinguish

1.      Both characterized by persistently elevated peripheral eosinophil counts

2.      Hypereosinophilia is polyclonal, whereas CEL is monoclonal

IV.              Diagnostic tools

a.       Cytochemical staining augments cytomorphology by identifying cytoplasmic chemical content generally associated with specific lineages

b.      Staining must be present in ≥3% of blasts based on a 200-cell count to be considered positive

c.       Cytochemical and histochemical staining

                                                               i.      Standard cytochemical panels typically include:

1.      Peroxidase (PO)

2.      Chloroacetate esterase (CAE)

3.      α-naphthyl-butyrate esterases (α-NBE)

4.      α-naphthyl-acetate esterases (α-NAE)

5.      Leukocyte alkaline phosphatase (LAP)

                                                             ii.      PO and SBB are generally positive in cells of the neutrophilic and, in some species, the eosinophilic lineages

                                                            iii.      CAE is usually positive in primary and secondary granules of neutrophilic, basophilic, and mast cell lineages

                                                           iv.      α-NAE and α-NBE are usually positive in monocytic cells, but lymphocytes, platelets, and megakaryocytes also are potentially positive

1.      Positivity in all but monocytes is resistant to sodium fluoride (NaF), whereas positivity in monocytes is inhibited by NaF

                                                             v.      Lymphocyte α-NBE positivity corresponds to lysosomal granules found in granulated lymphocytes, i.e., cytotoxic T cells and NK cells; therefore, positivity is localized to the Golgi zone

                                                           vi.      There are no enzymes specifically used to identify erythroid precursors

                                                          vii.      Plastic-embedding generally results in less shrinkage of cells

                                                        viii.      EM is required for distinguishing AUL from minimally differentiated AML and sometimes for identification of AMegL

                                                           ix.      SBB stain cannot be adapted for use on plastic-embedded sections

d.      Immunophenotyping

                                                               i.      Based on using monoclonal antibodies (MAbs) to detect lineage-specific and lineage-associated antigens

                                                             ii.      Most commercially available MAbs are designed for human or murine studies

1.      Cross-reactivity has been demonstrated

                                                            iii.      Immunophenotyping can be done on smears, tissue sections, or fluids

                                                           iv.      Most, but not all, MAbs can be adapted for flow cytometry

e.       Cytogenetics

                                                               i.      Required in the diagnostic work-up of myeloid neoplasms because of its value in determining treatment and prognosis

                                                             ii.      Karyotyping of canine patients is difficult because of almost identical chromosome morphologies, high canine diploid number (2n=78 in dogs), and resistance to banding

1.      No association of a specific abnormality with leukemia type or outcome

                                                            iii.      Karyotyping is easier in cats

V.                 Recommendations

a.       Myelofibrosis is common in certain diseases and results in difficulty in obtaining marrow aspirations

b.      AMLs with dysplasia are often secondary leukemias

c.       Most cases of AML, but not all, continue to be poor responders to medical intervention compared with lymphoid neoplasms