Acute Myeloid Leukemia (AML) is a stem cell disorder marked by the accumulation of immature hematopoietic cells, predominantly affecting adults. Its etiology includes genetic mutations, environmental factors such as radiation and chemical exposure, particularly in therapeutic settings, and is characterized by various cytogenetic abnormalities. Clinical presentation varies, with symptoms including fatigue, fever, and bleeding tendencies, and diagnosis often relies on laboratory findings and cytogenetic analysis.

1. ACUTE MYELOID LEUKEMIAS
DR NIKHIL P V

2. INTRODUCTION
 Acute leukemias are stem cell disorders
characterized by malignant neoplastic
proliferation and accumulation of immature
and non functional hematopoietic cells in the
bone marrow.
 The neoplastic cells show increased
proliferation and/or decreased apoptosis.
 If the defect primarily affects the common

3.  Acute myeloid leukemia (AML) is a
neoplastic disease characterized by
infiltration of the blood, bone marrow, and
other tissues by proliferative, clonal
undifferentiated cells of the hematopoietic
system.
 AML is the result of a sequence of somatic
mutations in a multipotential primitive
hematopoietic cell or, in some cases, a more

4.  Incidence : 1.5/100,000/year in infants decreases to
approximately 0.4 per 100,000 children ages 5 to 9 years,
increases gradually to 1.0 persons per 100,000 until age 25
years, and thereafter increases exponentially until the rate
reaches approximately 25/100,000 persons.
 AML accounts for 15 to 20 percent of the acute leukemias in
children and 80 percent of the acute leukemias in adults.
 Men > Women (4.5 : 3)

5. ETIOLOGY
 HEREDITY
 1) Chromosomal aneuploidy like Trisomy 21 noted in
Down syndrome
 2) Defective DNA repair, e.g., Fanconi anemia, Bloom
syndrome, and Ataxia telangiectasia
 3) Congenital neutropenia ie Kostmann syndrome
 4) Germline mutations of CCAAT/enhancer-binding
protein α (CEBPA), runt-related transcription factor 1 (RUNX1),
and tumor protein p53 (TP53) have also been associated with a
higher predisposition to AML

6.  RADIATION
 Peaks after 5 to 7 yrs of exposure.
 Therapeutic radiation alone seems to add little risk of AML but
can increase the risk in people also exposed to alkylating agents.
 CHEMICAL AND OTHER EXPOSURES
 Exposure to benzene, plastic, rubber, petroleum products, paint,
ethylene oxide, herbicides and pesticides can increase the risk.
 Smoking can also increase the risk

7.  DRUGS
 Anticancer drugs are the leading cause of therapy-associated
AML.
 Alkylating agent–associated leukemias occur on average 4–6
years after exposure, and affected individuals have aberrations in
chromosomes 5 and 7.
 Topoisomerase II inhibitor–associated leukemias occur 1–3 years
after exposure, and affected individuals often have aberrations
involving chromosome 11q23.
 Other agents like Chloramphenicol, phenylbutazone, and, less
commonly, chloroquine and methoxypsoralen.

8. MOLECULAR PATHOGENESIS
 AML results from a series of somatic mutations in
either a hematopoietic multipotential cell or
occasionally, a more differentiated, lineage-restricted
progenitor cell.
 Some cases of AML in younger individuals more
likely arise in a progenitor cell with lineage
restrictions.
 Other morphologic phenotypes and older patients
likely have disease that originates in a primitive
multipotential cell

9.  Core binding factor (CBF) has two subunits: CBF - Alpha and RUNX1
(formerlyAML1). Approximately 10 percent of AML cases have
translocations involving one of these two genes.
 These primary mutations are not sufficient to cause AML. Additional
activating mutations, for example, in hematopoietic tyrosine kinases,
FLT3 and KIT or in N-RAS and K-RAS, are required to induce a
proliferative effect in the affected primitive cell.
 Other protooncogene mutations occur in leukemic cells involving FES,
FOS, GATA-1, MPL, MYC, p53, NPM1, CEPBA.

10.  Because the mutant stem cell or early progenitor cell can
proliferate and retains the capability to differentiate, a wide variety
of phenotypes can emerge from a leukemic transformation.
 FLT3 encodes a tyrosine kinase receptor in normal myeloid and
lymphoid progenitors.
 Internal tandem duplications of FLT3 on chromosome 13 occurs
in approximately one-fourth to one-third of adult AML cases but
occurs more frequently in cases of AML with normal cytogenetic
patterns and monocytic phenotype.
 The FLT3-internal tandem duplication (ITD) mutation confers a
poor prognosis

11.  Deletions of all or part of a chromosome (eg., chromosome 5, 7,
or 9) or addition of chromosomes (eg., trisomy 4, 8, or 13) are
common cytogenetic abnormalities.
 Deletions in chromosomes 5 and 7 and complex cytogenetic
abnormalities are increased in frequency in older patients and
cases of AML following cytotoxic therapy.
 In acute promyelocytic leukemia, PML-RAR- fusion protein
represses retinoic acid-inducible genes, which prevent
appropriate maturation of promyelocytes.

12. CLINICAL FEATURES
 SYMPTOMS :
 Present with nonspecific symptoms initially.
 Fatigue is the first symptom
 Fever with or without infection will be present in approximately 10%
patients
 Bleeding, easy bruising
 occasionally, bone pain, lymphadenopathy, nonspecific cough,
headache, or diaphoresis
 Rarely patients may present with symptoms from a myeloid sarcoma
that is a tumor mass

13.  PHYSICAL FINDINGS :
 Splenomegaly, Hepatomegaly, Lymphadenopathy, Sternal
tenderness
 Evidence of infection and hemorrhage
 Severe gastrointestinal bleeding, intrapulmonary hemorrhage, or
intracranial hemorrhage occurs mostly in APL
 Infiltration of the gingivae, skin, soft tissues, or meninges with
leukemic blasts is characteristic of the monocytic subtypes.

14. LABORATORY FINDINGS
 PERIPHERAL BLOOD
 LEUCOCYTES
 - Elevated count,
 - 50% cases will have decreased or within reference
interval.
 - Counts ranges from <1000 to >100000/mul.
 - Presence of blasts > 20% suggests AL diagnosis.

 - Typically the myeloblasts seen in AML is 20mcM in
daimeter with nucleus composed primarily of
dispersed chromatin and variable prominent
nucleoli. Golgi apparatus is present but its not
easily visible. Granules may be present but not
visible by bright field microscopy.

15.  ERYTHROCYTES
 - Typically decreased and macrocytic,
 - RDW is increased,
 - Erthrocyte inclusions such as Howell-Jolly
bodies, Pappenheimer bodies and
basophilic stippling,
 -Nucleated RBCs can be present in
proportion to anemia or marrow damage.
 PLATELETS
 - Typically decreased
 - Hypogranular forms and sometimes giant platelets.
 - Qualitative platelet defect

16.  The presence of AUER RODS in blasts excludes ALL. Presence
of azurophilic granules is helpful in identifying myeloid nature of
the leukemia.
 Other abnormal findings in blood smear include monocytosis and
neutropenia.
 Neutrophils shows dysplasia including hyposegmentation ,
hypogranulation and small nuclei with hypercondensed
chromatin.
 Eosinophils ansd Basophils are mild to markedly elevated.

17.  BONE MARROW
 - Hypercellular with decreased fat content.
 - predominance of blasts and sometimes
with fibrosis.
 - Auer rods are present in BM blasts in half of
AMLcases
 OTHER LABORATORY FINDINGS
 - Hyperuricemia and increased lactate
dehydrogenase due to increased cell turn over
 - Hypercalcemia due to increased bone resorption
 - Increased serum and urine muramidase with
monocytic component

18. CELL LINEAGE IDENTIFICATION
 Three tools are mainly used,
 Cytochemistry
 Immunophenotyping
 Cytogenetics or molecular testing
 CYTOGENETICS
 Common stains used are Myeloperoxidase (MPO), Sudan Black B (SBB),
Naphthol AS-D Chloroacetate (specific esterase) and alpha naphthyl esterase
(non specific esterase).
 Granulocytic cells stain positive with MPO & SBB, whereas lymphoblasts are
negative. So differentiates AML & ALL.
 Granulocytic cell stains positive with specific esterase where as monocytic cell
lineage stain positive with non specific esterase. So esterases helps to
differenciate these two.

19.  IMMUNOPHENOTYPING BY FLOW
CYTOMETRY
 Its done when morphological appearance and
cytochemical reactions donot clearly define cell
lineage or when presence of more than one
neoplastic cell population is suspected.
 First panel should differenciate AML from B cell
ALL and T cell ALL., then second panel should
be used to subtype the AML into granulocytic,
monocytic, erythrocytic, and megakaryocytic
lineages.

20. CYTOGENETIC OR MOLECULAR ANALYSIS
 2/3 rd of patients with AML have detectable
cytogenetic abnormalities which includes
aneuploidies and translocations.
 Commonly observed aneuploidies include trisomi 8 &
21 , monosomy 7 & 21, and loss of x & y
chromosomes.
 Random cytogenetic abnormalities are observed in
AML with recurrent genetic abnormalities and therapy
related myeloid neoplasms which are characteristic.

21. AML WITH RECURRENT GENETIC ABNORMALITY
 This is when there is balanced or reciprocal
translocation occurs.
 In most cases rearrangements creates a fusion gene
encoding a new fusion protein.
 RTPCR has a higher sensitivity than cytogenetics for
diagnosing and following the progression of the
disease.
 This type of AML has better prognosis.

22.  1) AML WITH t(8;21)(q22;q22), RUNX1-RUNX1T1
 - 5 TO 10%
 - children and adults
 - Myeloblasts are large with abundant basophilic cytoplasm containing
numerous azurophilic granules, perinuclear clearing and auer rods. Some blasts will have very
large granules called pseudo Chediak Higashi granules. Nucleoli are prominent.
 - Promyelocytes, myelocytes and mature neutrophils with dysplasia are usually
present in bone marrow.
 - cell of origin is HSC
 - Cytochemical and immunophenotypic results are typical for myeloblasts ie it
is positive for CD13, 15, 33, 34, MPO, HLA DR
 - The t(8,21) results in reposition of RUNX1 with RUNX1T1( RUNX1-ETO) ,
results in a fusion protein, which is a transcriptional repressor which blocks the normal DNA
binding function of RUNX1, results in cellular proliferation and lack of cellular differenciation of
leukemic cells.

23. BMA SMEARS DEMONSTRATE LARGE BLASTS
WITH ABUNDANT BASOPHILIC CYTOPLASM
WITH FINE AZUROPHILIC GRANULES WITH
PERINUCLEAR HOF. NUCLEI ARE SLIGHTLY
EXCENTRIC WITH FINE CHROMATIN AND 2 TO 4

24.  2) AML with inv(16)(p13;q22) or t(16;16)(p13;22); CBFB-MYH11
 - Seen in 7% of patients
 - presents with granulocytic and monocytic maturation with
abnormal eosinophils in the bone marrow.
 - Presence of immature or basophilic granules in eosinophils is
the striking feature
 - Cell of origin is HSC
 - The immunophenotypic and cytochemical results shows
neutrophilic and monocytic lineages ie it is positive for CD13, 33, 34, MPO, HLA
DR
 - The inv(16) & t(16;16) both results in fusion of core binding
factor beta gene (CBFB) and smooth muscle myosin heavy chain gene
(MYH11). This protein binds to RUNX1 and represses its function as
transcription factor.

25. BMA SHOWS BOTH GRANULOCYTIC AND MONOCYTIC COMPONENTS
WITH MANY ABNORMAL EOSINOPHILIC PRECURSORS.
EOSINOPHILIC PRECURSORS SHOWS BOTH EOSINOPHILIC AND
BASOPHILIC GRANULES SHOWN BY ARROW
BM TREPHINE BIOPSY SHOWS HYPERCELLULAR MARROW
COMPOSED OF SHEETS OF LARGE BLASTS WITH VESICULAR NUCLEI
& MODERATE AMOUNT OF CYTOPLASM WITH NUMEROUS
EOSINOPHILIC PRECURSORS SHOWN BY ARROWS

26.  3)AML with t(9;11)(p22;q23); MLLT3-MLL
 - 2 to 5% of AML cases and 25% of
childhood AML cases
 - These are usually associated with
monocytic features ie mainly monoblasts and
promonocytes
 - Monoblasts and promonocytes
have pale basophilic cytoplasm, vacuolated,
nuclear chromatin is open with prominent
nucleoli

27. BMA SMEAR SHOWS MEDIUM TO LARGE BLASTS WITH MODERATE
TO ABUNDANT PALE BASOPHILIC AGRANULAR CYTOPLASM, WITH
OVOID TO INDENTED NUCLEI, FINE CHROMATIN, PROMINENT
NUCLEOLI RESEMBLES MONOBLASTS AND PROMONOCYTES
NON SPECIFIC ESTERASE POSITIVITY

28.  4) AML with t(15;17)(q22;q12); (PML/RARα)
 - 5 to 8 %, mostly middle aged adults
 - Acute promyelocytic leukemia with t(15;17) is an
AML in which abnormal promyelocytes predominate.
 - Both hypergranular and hypogranular presentations
can be seen.
 - most common clinical finding is bleeding and DIC is
very common.
 - cytochemical and immunophenotypical results are
positive for CD13,33 and MPO and negative for CD34 and
HLADR

29.  HYPERGRANULAR APL : mostly leucopenic,
most cells are promyelocytes with heavy azurophilic
granulation, cells with multiple bundled auer rods are
seen (FAGGOTS), nucleus is indented and bilobed,
anaemia and thrombocytopenia are typical.
 HYPOGRANULAR APL : Leukocytosis is
common, promyelocytes with agranular cytoplasm
with a bilobed reniform or multilobed nucleus with fine
nuclear chromatin and prominent nucleoli.

30. BMA SHOWS LARGE ABNORMAL PROMYELOCYTES WHICH ARE
HYPERGRANULAR, GRANULES ARE SO NUMEROUS AND DENSELY
PACKED THAT THEY ARE OBSCURING THE NUCLEUS. SOME CELLS
SHOWS AUER RODS (ARROW)
BMA SHOWS LARGE HYPOGRANULAR ATYPICAL PROMYELOCYTES
WITH ABUNDANT AGRANULAR CYTOPLASM

31. FAGGOT CELLS- MULTIPLE
AUER RODS IN LEUKEMIC
CELLS, ARRANGED AS
BUNDLES AND STALKS OR
CRISS CROSS PATTERN

32.  5) AML WITH t(6;9)(p23;q34); DEK-NUP214
 - 0.7 TO 1.8% AML, occurs in both adults and children.
 - presents with anaemia, thrombocytopenia, and sometimes
pancytopenia.
 - morphologically they resembe AMML, auer rods can be present
in one third of patients
 - marrow and peripheral blood basophilia is a consistent feature
 - Many cases shows granulocytic and erythroid dysplasia.
 -Fusion of DEK & NUP214 results in nucleoporin fusion protein
which acts as aberrant transcription factor.

33.  6)AML with inv3(q21;q26.2) or t(3,3)(q21;q26.2); RPN1 EVI1
 - 1 to 2 %, occurs in adults equally in males and females
 - it can arise denovo or from a prior MDS
 - peripheral blood platelets are increased and has atypical
megakaryocytes with mono or bilobated nuclei
 - patient presents with anaemia, elevated platelet count,
hepatospleenomegaly
 - fusion of RPN1 & EVI1 causes increased expression of
EVI1, results in increased cell proliferation and impaired cell
differenciation.

34.  7)AML with t(1;22)(p13;q13); RBM15-MKL1
 - < 1% of AML cases, in infants and
children
 - occurs denovo, and generally
shows maturation in the megakaryocytic
lineage
 - presents with marked

35. BMA SHOWS BLASTS WITH MODERATE AMOUNT OF PALE
BASOPHILIC , FINELY GRANULAR CYTOPLASM WITH CYTOPLASMIC
BLEBBING (ARROW) (MEGAKARYOBLASTS)
MPO POSITIVITY IN THE MYELOID PRECURSORS, BUT BLASTS WITH
BLEBBING ARE MPO NEGATIVE

36. BM TREPHINE BIOPSY SHOWING CD 41
POSITIVITY IN MEGAKARYOBLASTS AND
DYSPLASTIC MEGAKARYOCYTES

38. THERAPY RELATED MYELOID NEOPLASM
 It includes therapy related
 - Acute myeloid leukaemia (t-AML)
 - Myelodysplastic syndrome (t-MDS)
 - Myelodysplastic/myeloproliferative
neoplasm (t- MDS/MPN)
 Its a late complication of cytotoxic
chemotherapy or radiotherapy for a prior
maligancy.

39. AML WITH MYELODYSPLASIA RELATED
CHANGES
 This is a type of acute leukemia with morphological features of
myelodysplastic neoplasm.
 Prior history of MDS, MDS/MPN or MDS related cytogenetic
abnormality will be present.
 To classify as AML with myelodysplasia related changes by
morphology, the dysplasia must be present in 50% of cells in
atleast two cell lines.
 Cytochemistry and immunophenotypic results are positive for
MPO, SBB, Esterases and PAS.

40.  Dyserythropoiesis characterised by megaloblasts, karyorrhexis,
nuclear irregularity, and cytoplasmic vacuoles.
 Dysgranulopoiesis characterised by neutrophils with hypogranular
cytoplasm, hyposegmentation
 Dysmegakaryopoiesis characterised by micromegakaryocytes,
megakaryocytes with non lobated nuclei, or multiple nuclei.
 Chromosomal abnormality is similar to MDS , ie del of 7 and 5
chromosomes are most common.

41. ACUTE MYELOID LEUKEMIA - NOS
 This category includes cases of AML
that donot fulfil criteria for any of the
described groups.
 Sub categories are primarily
differenciated on morphology and
cytochemical features.

42.  1) AML WITH MINIMAL DIFFERENCIATION :
 - Rare, < 5% of all AML cases
 - lack of evidence of myeloid differenciation by morphology
(absence of granules) and by cytochemistry ( <3% blasts are positive for MPO &
SBB)
 - Blasts are usually large with small amount of pale blue
cytoplasm, nucleus has fine open chromatin with 1 or more prominent nucleoli.
 - Poor prognosis
 - Immunophenotype by flow cytometry demostrate myeloid
differenciation (CD 13, 33, 34, 38, 117 & HLA DR)
 - The cell of origin is hematopoietic precursor cell.

43. P.S SHOWS PRESENCE OF LARGE CELLS WITH SMALL
AMOUNT OF PALE GREY BLUE CYTOPLASM, WITH
FINE OPEN CHROMATIN AND PROMINENT NUCLEOLI
BM SHOWS INFILTERATION WITH LARGE BLASTS
WITH FEW ERYTHROID PRECURSORS

44. BM ASPIRATE SHOWS BLAST CELLS NEGATIVE FOR
MPO
BM TREPHINE BIOPSY SHOWS HYPERCELLULAR
MARROW WITH LARGE BLASTS WITH VESICULAR
NUCLEI AND PROMINENT NUCLEOLI

45.  2)AML WITHOUT MATURATION :
 - 5 to 10% of AML cases, occurs at any age but mostly seen in
adults
 - They usually presents with BM failure and leukocytosis
 - High percentage of bone marrow and peripheral smear blasts
without evidence of maturation is the characteristic feature
 - Predominent cell in peripheral blood and bone marrow is poorly
differentiated myeloblast, which are large with variable N:C ratio, blasts may
have azurophilc granules and rarely auer rods
 - BM show more than 90% cells which are myeloblasts with > 3%
of blasts are positive for MPO and SBB
 - Immunophenotype shows positivity for myeloid differenciation
(CD 13, 33, 34, 38, 117 & HLA DR)

46. PS SHOWS LARGE BLASTS WITH VARIABLE NC RATIO
WITH SCANT TO MODERATE AMOUNT OF PALE
BASOPHILIC CYTOPLASM
BMA SHOWS MANY LARGE BLASTS WITH SOME
SHOWING AZUROPHILIC GRANULES, WITH FEW
ERYTHROID PRECURSORS

47. BM TREPHINE BIOPSY SHOWING HYPERCELLULAR
MARROW INFILTERATED BY SHEETS OF BLASTS
BM TREPHINE BIOPSY SHOWING BLASTS WHICH ARE
POSITIVE FOR MPO

48.  3) AML WITH MATURATION :
 - 10% AML cases, occurs in all age
groups
 - characterised by > 20% blasts with
evidence of maturation to more mature
neutrophils ( >10% of cells are at different
stages of maturation ie promyelocytes,
myelocytes and metamyelocytes)

49. FIG A- PS SHOWS LARGE BLASTS WITH OVAL TO
INDENTED NUCLEI, PROMINENT 2 TO 3
NUCLEOLI, MOD AMT OF CYTOPLASM, WITH
FINE AZUROPHILIC GRANULES, WITH AUER
RODS(ARROW).
FIG B- BMA SHOWS NUMEROUS BLASTS WITH
SOME SHOWING AUER RODS, ONE MM IS ALSO
 ALPHA NAPHTHYL
CHLORACETATE
ESTERASE POSITIVITY
 BMA SHOWING BLAST
CELLS WITH AUER
RODS, WITH MATURING
MYELOID PRECURSORS

50.  4) AMML–ACUTE MYELOMONOCYTIC
LEUKEMIA :
 - 5 to 10% of AML cases
 - Characterised by proliferation of
both myelocytic and monocytic precursors
 -Peripheral blood shows increased
leukocyte count with monocytes and its

51.  - serum and urinary levels of muramidase are
usually elevated.
 - Monoblasts are large with abundant bluish
grey agranular cytoplasm shows pseudopods, and
vacuoles, nucleus is round convoluted with delicate
chromatin and one or more prominent nucleoli.
 - The cell of origin is Hematopoietic precursor
cell with the potential to differentiate into both neutrophil
and monocytic lineage (GMP)

52. BMA SHOWS MONOCYTOID CELLS (ARROW)
ALONG WITH A MYELOCYTE AND A
LYMPHOCYTE
PS SHOWS THREE LARGE MONOCYTOID CELLS WHICH HAS
ABUNDANT PALE BLUE AGRANULAR CYTOPLASM, OVOID TO
RENIFORM NUCLEI AND PROMINENT NUCLEOLI (ARROW)
BMA WITH DUAL ESTERASE STAIN, MONOCYTOID CELLS STAIN
POSITIVE FOR NON SPECIFIC ESTERASE (BLACK), AND MYELOID
PRECURSORS STAIN POSITIVE FOR CHLORACETATE ESTERASE
(RED)

53.  5) ACUTE MONOBLASTIC AND ACUTE MONOCYTIC
LEUKEMIA
 - seen in children and young adults
 - > 80% of leukemic cells are monocytic, which includes
monoblast, promonocytes and monocytes.
 - < 20% cells are neutrophilic component.
 - Most common clinical findings include weakness, bleeding and
diffuse erythematous skin rash
 - Extramedullary leukemic proliferation is characteristic
 -The cell of origin is Hematopoietic precursor cell committed to
monocytic differentiation (CFU-M)


54.  a) ACUTE MONOBLASTIC LEUKEMIA :
 - 5 to 8% of AML cases
 - majority of cells are monoblast
(>80%)
 - Monoblasts are large with
abundant basophilic agranular cytoplasm,
nucleus is round or oval with delicate
chromatin and one or more prominent
nucleoli. Cytoplasmic vacuolations may be

55. PS SHOWS PREDOMINENTLY MONOBLASTS WITH MODERATE
AMOUNT OF PALE BLUE CYTOPLASM, ROUND TO SLIGHTLY
INDENTED NUCLEI, FINE RETICULAR CHROMATIN, PROMINENT
NUCLEOLI. PROMINENT CYTOPLASMIC VACUOLATIONS ARE SEEN
BMA SHOWS PREDOMINENTLY MONOBLASTS, SOME SHOWS FINE
AZUROPHILIC GRANULES

56. PS SHOWS LARGE NUMBER OF PROMONOCYTES AND MONOCYTES
WITH ARROW SHOWING SINGLE MONOBLAST. PROMONOCYTES
HAVE ABUNDANT PALE BASOPHILIC CYTOPLASM AND IRREGULAR
CONVOLUTED NUCLEI AND PROMINENT NUCLEOLI
BMA SHOWS PROMONOCYTES (BLACK) AND MONOBLAST (RED)

57.  6) ACUTE ERYTHROID LEUKEMIA
 - < 5% of cases of AML with
predominent erythroid population.
 Two variants are seen,
 a) ERYTHROID/MYELOID VARIANT:
 - occurs in adults
 - BM shows >50% erythroid
precursors and >20% myeloblast in
nonerythroid population
 - Cell of origin is multipotential

58.  - Peripheral blood shows anemia with severe aniso poikilocytosis
with large number of nucleated RBCs that are dysplastic with megaloblastoid
nuclei or multinucleated cells in the more immature stages. Myeloblasts can also
be seen.
 - BM shows erythroblasts which are abnormal with giant
multilobular or multinucleated forms. It can also have nuclear budding,
fragmentation, cytoplasmic vacuoles, Howell Jolly bodies, ringed sideroblasts,
and megaloblastoid changes.
 - Dysplastic features of neutrophils, megakaryocytes and
Erythrophagocytosis of abnormal erythroblasts
 - Erythroblasts usually shows positivity with Glycophorin A (CD71)
or Hemoglobin A

59. BMA SHOWS TWO POPULATION OF CELLS, ONE IS BLASTS WITH ROUND TO OVOID NUCLEI, FINE NUCLEAR
CHROMATIN, PROMINENT NUCLEOLI,WITH MOD AMT OF CYTOPLASM WITH VACUOLATIONS (ARROW).
SECOND IS COMPRISED OF MANY ERYTHROBLASTS, WHICH ARE MEGALOBLASTOID WITH OPEN SIEVE LIKE
CHROMATIN AND IRREGULAR NUCLEAR MEMBRANE,
BMA SHOWS PREDOMINENTLY LARGE ERYTHROBLASTS

60.  7) ACUTE MEGAKARYOCYTIC LEUKEMIA
 - <5% of all AML cases, occurs in both adults and children
 - >50% of blasts are megakaryocytic lineage
 - mostly presents with cytopenias, sometimes present with
thrombocytosis
 - Dysplastic featues in neutrophils and platelets are common
 - Peripheral blood shows micromegakaryocytres and
undifferentiated blasts with cytoplasmic blebs
 - BM megakaryoblasts are medium to large with basophilic,
agranular cytoplasm, nucleus shows lacy chromatin and prominent nucleoli,
cells show distinct pseudopod formation
 - Immunophenotyping shows positivity for CD41, 61 &
occasionally, CD42 and cytochemistry shows positive for platelet peroxidase.

61. PS SHOWING BLASTS WITH CHARACTERISTIC CYTOPLASMIC
PLATELET BUDDING, THESE BLASTS ARE LARGE WITH HIGH NC
RATIO, SCANT TO MODERATE AMOUNT OF PALE BASOPHILIC
CYTOPLASM ,CONDENSED CHROMATIN & 1 TO 2 NUCLEOLI
CD 61 POSITIVITY IN MICROMEGAKARYOCYTES

62.  8)ACUTE BASOPHILIC LEUKEMIA
 - very rare, <1% of all AML cases
 - some cases develop as a blast transformation phase of CML
 - most cells are of basophilic lineage, blasts are of medium sized,
with high NC rato, cytoplasm contains basophilic granules, an oval to round
nucleus with dispersed chromatin and prominent nucleoli.
 - Most characteristic feature is metachromatic positivity with
toluidine blue in cytochemistry

 - Cell of origin is myeloid precursor committed to basophil lineage

63. BMA SHOWING BASOPHILIC PRECURSORS,
CONTAINING ABUNDANT BLUISH BLACK
GRANULES OBSURING NUCLEUS
PS SHOWS BLASTS WITH BASOPHILIC GRANULES
THE GRANULES IN THE BASOPHILIC PRECURSOR
STAINS WITH METACHROMATIC STAINS LIKE
TOLUIDINE BLUE

64.  9) ACUTE PANMYELOSIS WITH MYELOFIBROSIS
 - Very rare form of AML, occurs in adults
 - there will be panmyeloid proliferation and fibrosis
 - Dysplastic small megakaryocytes are characteristic
 - Diagnosis is by BM biopsy and immunohistology

65. CELL LINES, IT SHOWS DYSPLASTIC
MEGAKARYOCYTES IE
MICROMEGAKARYOCYTES(ARROW) WITH
FIBROSIS.
FIG 2 SHOWS RETICULIN STAIN SHOWS
INCREASE IN RETICULIN FIBRES

66. MYELOID SARCOMAS
 Also called Chloromas or Granulocytic
Sarcomas.
 Tumor mass of myeloblasts in extra
medullary sites or in bone.
 Can occur in AML or CML or
myeloproliferative or myelodysplastic
disorders.

67. TISSUE SHOWS INFILTERATION BY BLAST CELLS
FIG 2 LOW POWER VIEW OF MYELOID SARCOMA
SHOWS SHEETS OF ROUND MONOMORPHOUS
BLAST CELLS INFILTRATING THE SUB
CUTANEOUS TISSUE

68. MYELOID PROLIFERATIONS RELATED TO DOWN
SYNDROME
 Increased risk of AML in Down syndrome, 10 to 100 folds
 Two types
 1) Transient abnormal myelopoisis (TAM)
 - Rare disorder where blood and bone marrow
shows large number of blasts
 - Blasts have granular basophilic cytoplasm
with blebs and are CD41 +ve and
MPO –ve.
 - Spontaneous remission
 2) Acute megarkaryocytic leukemia of Down’s
 - Blasts are of megakaryocytic lineage with
CD41, 36 &61 positivity
 - GATA 1 gene mutation

69. BLASTIC PLASMACYTOID DENDRITIC CELL
NEOPLASM
 Rare, clinically aggressive hematopoietic neoplasm
 Derived from plasmacytoid dendritic cells
 Cutaneous and BM involvement and leukemic
dissemination
 Patients present with skin lessions like nodules, plaques
or bruises and lymphadenopathy is common
 Blasts are positive for CD4, 43, 56, 123, TCL1 & CLA and
negative for esterases and MPO

72. TREATMENT
 Treatment of the newly diagnosed patient with AML is usually
divided into two phases, induction and postremission
management.
 INDUCTION CHEMOTHERAPY
 The most commonly used induction regimens (for patients other
than those with APL) consist of combination chemotherapy with
cytarabine and an anthracycline (e.g., daunorubicin, idarubicin,
mitoxantrone).
 POSTREMISSION THERAPY
 For younger patients, most studies include intensive
chemotherapy and allogeneic or autologous hematopoietic stem
cell transplantation

73.  TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA
 Tretinoin
 Arsenic trioxide
 Combinations of tretinoin, arsenic trioxide, and/or chemotherapy
and/or gemtuzumab, ozogamicin have shown favorable
responses in high-risk APL patients at diagnosis
 Followed by autologous or allogeneic HSCT.

74. REFERENCES
 ROBBINS & COTRAN. PATHOLOGIC BASIS OF DISEASE, 9TH
EDITION
 MCKENZIE AND J.L. WILLIAMS CLINICAL LABORATORY
HEMATOLOGY, 3RD EDITION
 WILLIAMS HEMATOLOGY, 8TH EDITION
 HARRISONS’S PRINCIPLES OF INTERNAL MEDICINE, 19TH
EDITION.
 DR TEJINDAR SINGH, HEMATOPATHOLOGY ATLAS
 INTERNET SOURCES

75. THANK YOU