D R . P R I YA N K A YA D AV
D R . V A I B H AV M O D I
CASE REPORT
MIMICKING APML
A DIAGNOSTIC CONFUSION

LAYOUT
• Case report
• Investigations
• Peripheral smear
• Bone marrow
• Differential Diagnosis
• Further Approach

CASE REPORT
• 3 year old female patient
• Complaints :
 Bluish red rashes over body
 Bleeding from nose and gums
 Subconjunctival bleed on minor trauma
 Reddish brown stools
since 2 days
No family history of bleeding

CASE REPORT…
• On examination:
 Pallor
 Ecchymoses & purpuric rashes all over body
 No oraganomegaly/ lymphadenopathy
• CBP Platelets –
Hemoglobin – 9.3 g/dl
Total WBC - 22,600 cells/cumm
Differential - N 36 L60 E02 M02 B00
Platelets - 13,000 /cumm

• BT : > 10 min; CT: 5.5 min
• PT, APTT : WNL
• LFT & RFT : WNL
CASE REPORT…

PS COMMENT
Hb: 9.3g/dl
RBC series:
• Mild anisopoikilolocytosis
with moderate hypo-
chromia
• Nucleated RBCs –
4/100 WBCs

PS COMMENT
WBC series:
• Total WBC -
22,600 cells/cu mm
• Differential - N
36 L60 E02 M02 B00
• Shift to left seen in myeloid
series
• Occassional Blast cells
seen

PS COMMENT
BLAST CELLS ?
myeloblast
• Some had coarse
azurophilic granules
• At places, auer rod like
structures in cytoplasm
? Artifact
? Toxic granules
? Promyelocytes

PS COMMENT
Platelets:
• Markedly reduced – less
than 10,000/cumm
• Morphologically normal

PS COMMENT- IMPRESSION
• Clinical picture ; age, bleeding **
• Anemia
• Leukocytosis with shift to the left**
• Thrombocytopenia
? Acute Promyelocytic Leukemia
? Infection
Important to rule out Acute Promyelocytic Leukemia
- Hematological emergency
Our Diagnosis: Infection
Follow up was advised.

FURTHER CLINICAL COURSE
• Antibiotics (Cephalosporins) and supportive treatment
• 6 transfusions (2 PRCs and 4 RDP)
• In one week, no improvement
• Platelet count still low
Patient was sent for review and for Bone Marrow Examination

REPEAT PERIPHERAL SMEAR

REPEAT PERIPHERAL BLOOD/ SMEAR
1st PS REPEAT PS
Hemoglobin 9.3gm/dl 8.9 g/dl
RBC Series Normocytic
hypochromic
Normocytic
hypochromic
Total WBC 22,600 cells/cumm 17,600 cells/cumm
Differential N 36 L60 E02 M02 B00 N 65 L30 E02 M03 B00
Blasts +
Promyelocytes
11% 4%
Toxic granulation in
neutrophils
Few Large number
Platelets Markedly reduced Markedly reduced

BONE MARROW ASPIRATION
• Marrow- normocellular
• M:E ratio – 2:1
• Eryhthroid series:
Reaction pred.
normoblastic with
megaloblastoid
changes
Marrow - easy to aspirate

BONE MARROW ASPIRATION
Myeloid series-
• Shift to left – (myelocytes
and metamyelocytes –
38%)
• Myelocytes and
metamyelocytes showing
heavy toxic granulations
• Percentage of blasts and
promyelocytes– 08%
• No Auer rods seen in blasts

BONE MARROW ASPIRATION
Megakaryocytes
• Increased in number
• Few loose clusters
• Few showing
cytophagocytosis

BONE MARROW ASPIRATION
Plasma cells
• Within normal limits
Reticulum cells
• Within normal limits
Iron : 3 (+++)
Hemoparasite : none

DIFFERENTIAL DIAGNOSIS
Diagnosis: ITP with INFECTION
D/D:
• APML
• ALL
• HEMATOGONES
• VIRAL INFECTION
• Myelodysplastic Syndrome

ACUTE ITP
Points FOR:
• Age
• Clinical presentation
• PS: Thrombocytopenia
• BM:
 ↑ megakaryocytes
 Morphology of
megakaryocytes
 Loose clusters

INFECTION/ LEUKEMOID
REACTION
Points FOR:
• PS:
 Leukocytosis
 Shift to left
 Toxic granulations
 Reactive lymphocytes
• Bone Marrow:
 Shift to left
 Toxic granulations
 Cytophagocytosis
 Increased megakaryocytes
 BM iron increased
Points AGAINST:
• Platelet count – variable
• Absence of fever/sepsis

APML/AML
Points FOR:
• Clinical presentation
• Leukocytosis
• Morphological
• Blasts, promyelocyts along
with other myeloid
precursors seen in PS
Points AGAINST:
• Age of presentation
• Hepatosplenomegaly of
various degree
• Blasts >20% of bone marrow
non-erythroid cells
• Suppression of erythroid and
megakaryocytic series

ALL
Points FOR:
• Age
• Clinical presentation
Points AGAINST:
• No Hepatosplenomegaly
• No Lymphadenopathy
• PS: Pancytopenia
• BM: Suppression of erythroid
megakaryocytic and myeloid
series
• Blasts >20% of bone marrow
non-erythroid cells
• Morphology of blast cells
L1 L2 L3

LYMPHOBLASTS VS MYELOBLASTS
LYMPHOBLAST MYELOBLAST
MORPHO-
LOGY
CYTO-
CHEMISTRY
PAS + (block)
Acid phosphatse + (T-cell)
PAS –
diffuse fine +ve in
M6,M7, M3*
MPO, Sudan Black, NSE +
I MMUNO-
PHENOTYPIN
G
B-cell - Strong CD19 and atleast 1 of the
following strongly expressed: CD79a,
cyCD22, CD10
T-cell - Cytoplamic CD3 or Surface CD3
MPO or
Monocytic differentiation (at least 2 of
the following NSE,
CD11C, CD14, CD64)
Only immunophenotyping permits a positive diagnosis of ALL

HEMATOGONES
• BM B-lymphocyte
precursors.
• Present in neonates, young
children , infection, post BM
transplant
• Diagnostic confusion with
ALL
• Immunophenotyping

MYELODYSPLASTIC SYNDROME
Points FOR:
• Bicytopenia
• Blasts ≥ 5%
Points AGAINST:
• Age
• PS: evidence of dysplasia
• BM: evidence of
dysplasia in >10% of
erythroid, granulocyte
precursors and
megakaryocytes

IMPRESSION
Peripheral smear along with bone marrow was
suggestive of -
IDIOPATHIC THROMBOCYTOPENIC PURPURA
with evidence of INFECTION

FURTHER INVESTIGATION
• NAP score
• Cytochemistry
• Immunophenotyping
• Cytogenetics
• Molecular genetics

SUMMARY
• Not every bleeding is APML
• Bleeding complaints
 Age,
 Family history
 Site of bleeding
 Preceding infection
 Lymphadenopathy and organomegaly
 Careful examination of PS
 BM Examination if indicated