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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

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CASE REPORT -SEMINAR APML.pptx

  • 1. 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
  • 2. LAYOUT • Case report • Investigations • Peripheral smear • Bone marrow • Differential Diagnosis • Further Approach
  • 3. 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
  • 4. 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
  • 5. • BT : > 10 min; CT: 5.5 min • PT, APTT : WNL • LFT & RFT : WNL CASE REPORT…
  • 6. PS COMMENT Hb: 9.3g/dl RBC series: • Mild anisopoikilolocytosis with moderate hypo- chromia • Nucleated RBCs – 4/100 WBCs
  • 7. 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
  • 8. PS COMMENT BLAST CELLS ? myeloblast • Some had coarse azurophilic granules • At places, auer rod like structures in cytoplasm ? Artifact ? Toxic granules ? Promyelocytes
  • 9. PS COMMENT Platelets: • Markedly reduced – less than 10,000/cumm • Morphologically normal
  • 10. 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.
  • 11. 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
  • 13. 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
  • 14. BONE MARROW ASPIRATION • Marrow- normocellular • M:E ratio – 2:1 • Eryhthroid series: Reaction pred. normoblastic with megaloblastoid changes Marrow - easy to aspirate
  • 15. 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
  • 16. BONE MARROW ASPIRATION Megakaryocytes • Increased in number • Few loose clusters • Few showing cytophagocytosis
  • 17. BONE MARROW ASPIRATION Plasma cells • Within normal limits Reticulum cells • Within normal limits Iron : 3 (+++) Hemoparasite : none
  • 18. DIFFERENTIAL DIAGNOSIS Diagnosis: ITP with INFECTION D/D: • APML • ALL • HEMATOGONES • VIRAL INFECTION • Myelodysplastic Syndrome
  • 19. ACUTE ITP Points FOR: • Age • Clinical presentation • PS: Thrombocytopenia • BM:  ↑ megakaryocytes  Morphology of megakaryocytes  Loose clusters
  • 20. 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
  • 21. 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
  • 22. 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
  • 23. 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
  • 24. HEMATOGONES • BM B-lymphocyte precursors. • Present in neonates, young children , infection, post BM transplant • Diagnostic confusion with ALL • Immunophenotyping
  • 25. 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
  • 26. IMPRESSION Peripheral smear along with bone marrow was suggestive of - IDIOPATHIC THROMBOCYTOPENIC PURPURA with evidence of INFECTION
  • 27. FURTHER INVESTIGATION • NAP score • Cytochemistry • Immunophenotyping • Cytogenetics • Molecular genetics
  • 28. 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

Editor's Notes

  1. Usually pancytopenia in AML/ALL pts..here bicytopenia Family history Bleeding disorder – m.c hemophilia – but this is girl Then ALL – pancytopenia with blasts –
  2. Marrow – difficulty to aspirate in cases of ALL
  3. AML – Anemia, bleeding manifestations and infection APML -
  4. T(8:21); 15:17; 16:16; inv 16; myeloid sarcoma
  5. Morphologically hematogones are distinct lymphoid cells with condensed and homogeneous chromatin, and scant cytoplasm. These cells can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders.  They varied from 10 to 20 µ in diameter, with smaller cells predominating. The nucleus is round or oval and can exhibit one or more indentations or shallow clefts. Nucleoli were absent or small and indistinct. There is generally scant or no discernible cytoplasm; when present, cytoplasm is moderately to deeply basophilic and devoid of granules, inclusions, or vacuoles. There is often a variety of size and cytologic features that blends with those of mature lymphocytes. Frequently a portion of the hematogones exhibited features indistinguishable from lymphoblasts of ALL. Haema- togones tend to express TdT strongly and CD10 and CD19 weakly, whereas the reverse pattern of reac- tivity is seen with ALL blast cells [42]. The detection of persisting cells with an aberrant combination of antigens is more reliable, as is polymerase chain reaction (PCR) analysis for rearranged immunoglobulin heavy chain (IGH) or T-cell receptor (TCR) genes (see below).
  6. Aplastic anemia is characterized by bone marrow hypoplasia with failure to form all 3 lineages resulting in peripheral cytopenia MDS: Morphologcally shows impairment of proliferation and differentiation Hb<10; ANC < 1800/cumm; Platelet < 1 lakhs