Myeloid Session: Case Presentation IAP Adam Bagg Jordan - - PowerPoint PPT Presentation

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Myeloid Session: Case Presentation IAP Adam Bagg Jordan - - PowerPoint PPT Presentation

May 24, 2023 165 likes •455 views

Myeloid Session: Case Presentation IAP Adam Bagg Jordan University of Pennsylvania Philadelphia October 2018 History 86yearold woman No significant past medical history Lives alone, rakes her own leaves Dizzy for

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Myeloid Session: Case Presentation

Adam Bagg University of Pennsylvania Philadelphia

IAP Jordan October 2018

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SLIDE 2

History

  • 86‐year‐old woman
  • No significant past medical history
  • Lives alone, rakes her own leaves
  • Dizzy for several days
  • Intermittent fevers
  • Loss of appetite
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SLIDE 3

Laboratory

  • WBC: 74,000/µl (was 6,000/µl 8 months previously)

– 10% neutrophils – 15% lymphocytes – 4% monocytes – 2% eosinophils – 13% bands – 3% metamyelocytes – 8% myelocytes – 37% promyelocytes – 2% blasts

  • Platelets: 81,000/µl
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SLIDE 4

Timeline of Events

Day 0 8 High Dose Hydroxyurea Presentation (outside hospital) Peripheral blood smear not available for review WBC and differential: 74 k/µl, 37% promyelo, 2% blast, 2% eos FISH: t(15;17) PML‐RARA [3/200] Bone marrow biopsy #1 Therapy

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Bone Marrow Aspirate #1

Marked myeloid left shift with increased promyelocytes, myelocytes, and eosinophil precursors. No increase in blasts. No morphologically classic leukemic promyelocytes. Wright‐Giemsa, 50x

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SLIDE 6

Bone Marrow Biopsy #1

Markedly hypercellular H&E 5x

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SLIDE 7

Bone Marrow Biopsy #1

Prominent bone marrow eosinophilia H&E 50x

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SLIDE 8

Bone Marrow Biopsy #1

Numerous immature myeloid precursors H&E 50x

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SLIDE 9
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SLIDE 10

Genetic Studies

  • Peripheral blood

– RT‐PCR for BCR‐ABL1: negative – JAK2 V617F mutation: negative – FISH for t(15;17) PML‐RARA:

  • Low positive [3/200]
  • Bone marrow #1

– Cytogenetics:

  • 46,XX,t(8;9)(p22;p24)[20]
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SLIDE 11

Timeline of Events

Day 0 8 12 21 35 High Dose Hydroxyurea Presentation (outside hospital) Peripheral blood smear not available for review WBC and differential: 74 k/µl, 37% promyelo, 2% blast, 2% eos FISH: t(15;17) PML‐RARA [3/200] Bone marrow biopsy #1 Left‐shifted, eosinophilia 46,XX,t(8;9)(p22;p24)[20] Transfer from outside hospital Peripheral blood smear #1 WBC and differential: 51.4 k/µl, 2% promyelo, 3% blast, 7% eos Therapy

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SLIDE 12

Peripheral Blood #1

Wright‐Giemsa, 100x Eosinophilia including eosinophilic precursors (C) A B C Blasts without morphologic features

  • f leukemic promyelocytes, few

granules (A,B)

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Karyotype (Peripheral Blood #1)

46,XX,t(8;9)(p22;p24)[27]

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SLIDE 14

FISH (Peripheral Blood #1)

t(15;17) PML‐RARA [2/200 interphase cells]

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SLIDE 15

PML‐RARA, PML Intron 3 Breakpoint

Identified by RT‐PCR

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Timeline of Events

Day 0 8 12 21 35 All‐Trans Retinoic Acid (ATRA) Arsenic Trioxide (ATO) Presentation (outside hospital) Peripheral blood smear not available for review WBC and differential: 74 k/µl, 37% promyelo, 2% blast, 2% eos FISH: t(15;17) PML‐RARA [3/200] Bone marrow biopsy #1 Left‐shifted, eosinophilia 46,XX,t(8;9)(p22;p24)[20] Transfer from outside hospital Peripheral blood smear #1 WBC and differential: 51.4 k/µl, 2% promyelo, 3% blast, 7% eos Bone marrow biopsy #2 Therapy High Dose Hydroxyurea

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SLIDE 17

Bone Marrow Biopsy #2

Markedly hypercellular H&E 5x

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SLIDE 18

Bone Marrow Biopsy #2

Numerous immature cells, few eosinophils H&E 50x

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Genetic Studies

  • Bone marrow #2 (hemodilute aspirate)

– FISH: negative for t(15;17) PML‐RARA – RT‐PCR: negative for t(15;17) PML‐RARA – Karyotype: 46,XX[6]

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SLIDE 20

Timeline of Events

Day 0 8 12 21 35 High Dose Hydroxyurea All‐Trans Retinoic Acid (ATRA) Arsenic Trioxide (ATO) Presentation (Outside Hospital) Peripheral Blood (Smear Not Available For Review): WBC: 74 k/µl, 37% Promyelo, 2% Blast, 2% Eos FISH: t(15;17) PML‐RARA [3/200] Transfer From Outside Hospital Peripheral Blood #1 WBC: 51.4 k/µl, 2% Promyelo, 3% Blast, 7% Eos Bone Marrow Biopsy #2 Hemodilute aspirate Left‐shifted biopsy 46,XX[6] PML‐RARA negative Bone marrow biopsy #1 Left‐shifted, eosinophilia 46,XX,t(8;9)(p22;p24)[20]

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SLIDE 21

Timeline of Events

Day 0 8 12 21 35 Presentation (Outside Hospital) Peripheral Blood (Smear Not Available For Review): WBC: 74 k/µl, 37% Promyelo, 2% Blast, 2% Eos FISH: t(15;17) PML‐RARA [3/200] Transfer From Outside Hospital Peripheral Blood #1 WBC: 51.4 k/µl, 2% Promyelo, 3% Blast, 7% Eos Therapy stopped due to renal failure. Hospice care: comfort measures only Bone marrow biopsy #1 Left‐shifted, eosinophilia 46,XX,t(8;9)(p22;p24)[20] Bone Marrow Biopsy #2 Hemodilute aspirate Left‐shifted biopsy 46,XX[6] PML‐RARA negative High Dose Hydroxyurea All‐Trans Retinoic Acid (ATRA) Arsenic Trioxide (ATO)

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Potential Effect of Arsenic Trioxide

On Eosinophilia and t(8;9) PCM1‐JAK2

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

Eosinophils (Absolute)

Days After Transfer From Outside Hospital

All‐Trans Retinoic Acid (ATRA) Arsenic Trioxide (ATO)

Eosinophils (x1000)/µl

t(8;9)[27] 46,XX[6]

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Summary

  • Available morphology alone (that may have been modified by therapy) did

not differentiate acute leukemia from myeloproliferative neoplasm

  • Identification of t(8;9) PCM1‐JAK2 facilitated the diagnosis of a myeloid

neoplasm with eosinophilia and PCM1‐JAK2

  • t(15;17) PML‐RARA prompted diagnosis of acute promyelocytic leukemia

(APL) despite the absence of classic morphology (and absence of initial peripheral blood smear for review)

  • Unclear whether APL represented clonal evolution of the “chronic”

myeloid neoplasm or whether findings represent a composite neoplasm (either way, most unusual)

  • Both the t(8;9), present in 100% of metaphases, as well as peripheral

blood and marrow eosinophilia, disappeared following brief Rx with ATO (± ATRA), hinting at the possible therapeutic potential of this agent

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SLIDE 24

Summary

  • Available morphology alone (that may have been modified by therapy) did

not differentiate acute leukemia from myeloproliferative neoplasm

  • Identification of t(8;9) PCM1‐JAK2 facilitated the diagnosis of a myeloid

neoplasm with eosinophilia and PCM1‐JAK2

  • t(15;17) PML‐RARA prompted diagnosis of acute promyelocytic leukemia

(APL) despite the absence of classic morphology (and absence of initial peripheral blood smear for review)

  • Unclear whether APL represented clonal evolution of the “chronic”

myeloid neoplasm or whether findings represent a composite neoplasm (either way, most unusual)

  • Both the t(8;9), present in 100% of metaphases, as well as peripheral

blood and marrow eosinophilia, disappeared following brief Rx with ATO (± ATRA), hinting at the possible therapeutic potential of this agent

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SLIDE 25

Summary

  • Available morphology alone (that may have been modified by therapy) did

not differentiate acute leukemia from myeloproliferative neoplasm

  • Identification of t(8;9) PCM1‐JAK2 facilitated the diagnosis of a myeloid

neoplasm with eosinophilia and PCM1‐JAK2

  • t(15;17) PML‐RARA prompted diagnosis of acute promyelocytic leukemia

(APL) despite the absence of classic morphology (and absence of initial peripheral blood smear for review)

  • Unclear whether APL represented clonal evolution of the “chronic”

myeloid neoplasm or whether findings represent a composite neoplasm (either way, most unusual)

  • Both the t(8;9), present in 100% of metaphases, as well as peripheral

blood and marrow eosinophilia, disappeared following brief Rx with ATO (± ATRA), hinting at the possible therapeutic potential of this agent

slide-26
SLIDE 26

Summary

  • Available morphology alone (that may have been modified by therapy) did

not differentiate acute leukemia from myeloproliferative neoplasm

  • Identification of t(8;9) PCM1‐JAK2 facilitated the diagnosis of a myeloid

neoplasm with eosinophilia and PCM1‐JAK2

  • t(15;17) PML‐RARA prompted diagnosis of acute promyelocytic leukemia

(APL) despite the absence of classic morphology (and absence of initial peripheral blood smear for review)

  • Unclear whether APL represented clonal evolution of the “chronic”

myeloid neoplasm or whether findings represent a composite neoplasm (either way, most unusual)

  • Both the t(8;9), present in 100% of metaphases, as well as peripheral

blood and marrow eosinophilia, disappeared following brief Rx with ATO (± ATRA), hinting at the possible therapeutic potential of this agent

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SLIDE 27

Summary

  • Available morphology alone (that may have been modified by therapy) did

not differentiate acute leukemia from myeloproliferative neoplasm

  • Identification of t(8;9) PCM1‐JAK2 facilitated the diagnosis of a myeloid

neoplasm with eosinophilia and PCM1‐JAK2

  • t(15;17) PML‐RARA prompted diagnosis of acute promyelocytic leukemia

(APL) despite the absence of classic morphology (and absence of initial peripheral blood smear for review)

  • Unclear whether APL represented clonal evolution of the “chronic”

myeloid neoplasm or whether findings represent a composite neoplasm (either way, most unusual)

  • Both the t(8;9), present in 100% of metaphases, as well as peripheral

blood and marrow eosinophilia, disappeared following brief Rx with ATO (± ATRA), hinting at the possible therapeutic potential of this agent