Hematology Conference

Slide Review

August 11, 2008

 General Data
 E.I. 42 year old, male
 Married
 Filipino
 Mechanic/welder
 Roman Catholic
 Resides in Nueva Ecija

 CC: Dizziness

Date of Admission : 7/08/08, 6am

Date of Interview : 7/08/08, 7am
Source & Reliability : Patient 85% reliability
4 weeks PTA: HPI
•Hematoma on left shoulder after
trauma (grew in size, longer time
than usual to resolve)

•Bleeding gums after using a

toothpick (bled for two days)

•No fever, abdominal pain, epistaxis

nor jaundice

•No medications taken, nor consult

done
3 weeks PTA: HPI
•Dizziness (lightheadedness)
during minimal activities

•Accompanied by weakness, easy

fatigability and fever (40.8C)

•Paracetamol 500mg/tab  slight

relief from fever

•Large hematoma of posterior left

thigh with no accompanying trauma
 1 week PTA: HPI
•Persistance of symptoms
•Worsening of dizziness and
weakness

•Consult at local hospital

•CBC and urinalysis
•Dx: Aplastic anemia
•Transfused 4 ‘u’ of platelet
concentrate and 5 ‘u’ of FWB

•Referred to USTH for specialist

ADMISSION
 Review of Systems

 General  Ears
(-) weight change (-) hearing difficulties
(-) chills (-) infection
(-) sweats (-) tinnitus
(-) discharge
 Skin  Eyes
(-) rashes (-) redness
(-) sores (-) itchiness
(-) itching (-) glaucoma
(-) dryness (-) cataracts
(-) color changes
(-) changes in hair or nails
 Review of Systems

 Nose  Respiratory
(-) cold (-) hemoptysis
(-) discharges (-) wheezing

 Throat/Mouth  Gastrointestinal
(-) sore throat (-) melena and hematochezia
(-) hoarseness (-) diarrhea/constipation
(-) jaundice
 Neck
(+) submandibular mass, left (-)  Cardiac
swollen glands (-) Chest pain
(-) stiff neck (-) Orthopnea
(-) Palpitatons
 Review of Systems

 Vascular  Psychiatric
(-) claudication (-) tension
(-) varicosities (-) anxiety

 Genitourinary  Neurologic
(-) urinary frequency (+) headache
(-) hematuria (-) fainting
(-) dysuria (-) seizures
(-) motor or sensory loss
 Musculoskeletal (-) numbness
(-) stiffness
(-) muscle pain
(-) joint pain
 Past Medical History

 Immunizations: Unrecalled immunizations

 Operations: (–)
 Illnesses: 2003 gouty arthritis – relieved by
Allopurinol and Colchicine
 Allergies: No known allergies to food or drugs
 No medications or vitamins
 (-) DM, HPN, Hepatitis
 Personal and Social History

 Smoker: 24 pack year

 Alcohol beverage drinker – 3x/week (at most 2
bottles of beer each)
 Used methamphetamine (2002)
 Diet
 Mixed, mostly seafood
 Water Source  MWSS, not boiled
 Food Source  cooks food at home
 Personal and Social History

 (+) Travel to Aurora province

 Chemical exposure (at work) – acetylene, benzene
 Good family support/relationship, lives with wife
and 5 children
 Good relationship with peers
 Family History

 (+) Leukemia – cousin

 (+) Breast Cancer – cousin
 (–) HPN
 (–) DM
 (–) TB
 (–) Stroke
 PE on Admission

 BP: 110/80
 PR: 88 regular
 RR: 19 regular
 Temp: 36.7 C
 BMI: 25.7
 Wt: 70 kg
 Ht: 165 cm
 Physical Exam
 General
 Conscious, coherent, ambulatory, not in CP distress
 Skin
 Warm, moist skin, (-) jaundice, no active dermatoses
 HEENT
 Pink palpebral conjunctiva, anicteric sclerae, pupils 2–3mm ERTL,
no tragal tenderness, no nasoaural discharge
 (+) Gum bleeding on lower incisors, Moist buccal mucosa, non
hyperemic PPW, tonsils not enlarged
 Supple neck, (+)1.5 x 1.5 cm, left palpable, tender, submandibular
lymph node, thyroid not enlarged
 Physical Exam

 Breasts
 Symmetrical, no masses, no discharge
 Thorax/Lungs
 Symmetrical chest expansion, no retractions, equal tactile and
vocal fremiti, no crackles/wheezes
 Cardiovascular
 Adynamic precordium, AB 5th LICS MCL, S1 > S2 at apex, S2 >S1
at base, (-) murmur
 Physical Exam

 Abdomen
 Flabby abdomen, soft, NABS, no bruits
 No tenderness
 Non-palpable liver edge
 Traube’s space not obliterated
 No CVA tenderness
 Physical Exam

 Musculoskeletal
 No muscle atrophy , no swelling in all extremities
 No tenderness, swelling nor limitation in motion
 Extremities
 no cyanosis, clubbing
 Pulses full and equal
 (-) Edema
 Physical Exam

 Neurologic
 Mental Status: Conscious, coherent, oriented to time, person and
place, follows commands.
 Cranial nerves: all intact
 Motor: No muscle atrophy/hypertrophy, no fasciculations, tremors,
rigidity, spasticity
 MMT: 5/5 on all extremities
 Cerebellar: can do FTNT, APST
 Gait: normal 5/5 5/5
 No sensory deficits
 DTR's ++
 No babinski, No nuchal rigidity
5/5 5/5
 Salient Features

Subjective data
 (+) gum bleeding
 (+) dizziness
 (+) weakness
 (+) easy fatigability
 (+) fever of 40.8 deg C
 Salient Features

 Objective data
 (+) gum bleeding on lower incisors
 (+) 1.5x1.5 cm palpable, tender submandibular lymph node,
left
Clinical Assessment

t/c Acute Leukemia

LABORATORIES
 CBC 7/8 7/9 7/10 7/11 7/12 7/13 7/15 7/17 7/18 7/20

Hgb 81 103 98 98 99 98 96 88 78 74

Hct 0.23 0.29 0.27 0.28 0.26 0.27 0.27 0.25 0.23 0.21

MCV 85.4 85.6 85.8 85.4 82.6 80.1 80.60 80.0 80.7 79.6

MCH 30.7 30.4 30.8 30.2 32 28.6 28.80 28.5 27.3 28.2

MCHC 36 35.5 35.9 35.3 38.8 35.7 35.70 35.6 33.8 35.4

Plt 20 40 20 40 80 80 150 40 140 40

WBC 3.7 4.9 3.5 5.4 5.2 4.4 4.20 3.6 5.4 9.9

0.09 0.06 0.05 0.31 0.13 0.13 0.05 0.12 0.17 0.10
Neutrophil
Metamyel 0.5 0.04 0.01 0.05 0.03 0.07 0.02 0.07 0.04
ocytes
Bands 0.01 0.02 0.01 0.01 0.02

0.03 0.02 0.04 0.24 0.1 0.05 0.05 0.09 0.08 0.06
Segmente
d 0.66 0.31 0.45 0.46 0.66 0.78 0.92 0.54 0.58 0.46
Lymphocy
tes
Blast 0.24 0.53 0.43 0.1 0.06 0.03 0.12 0.05

Myelocyte 0.08 0.05 0.12 0.15 0.04 0.02 0.02 0.11

Promyelocyte 0.03 0.16 0.16 0.28

 CBC 7/22 7/23 7/24 7/25 7/26 7 7/27 7/29 7/30 7/31 8/1 8/2
/27 ()
Hgb 81 88 102 99 96 ()
99 94 94 87 95 86 95

RBC 2.87 2.99 3.54 3.35 3.98 3.32 3.25 3.27 3.02 3.27 2 3.27
.96
Hct 0.23 0.24 0.29 0.28 0.27 0.27 0.27 0.27 0.25 0.27 0 0.27
.24
MCV 81.5 80.8 82.6 82.5 83.4 82.4 84.0 82.82 82.2 82.9 8 82.0
1.7
MCH 28.1 29.4 28.9 29.4 29.2 29.7 28.9 28.6 28.7 29.1 2 29.1
9.0
MCHC 34.5 36.4 35.0 35.6 35.0 36.1 34.5 34.6 34.9 35.1 3 35.5
5.5
RDW 17.8 17.6 17.6 17.6 17.0 17.9 16.3 17.8 17.7 17.5 17 17.8

Plt 120 60 40 40 40 20 100 80 60 80 40 152

WBC 16.2 37.5 36.5 32.8 33.3 34.8 25.5 13.5 6.4 3.10 1 2.90
.60
Neutrophil 0.24 0.64 0.33 0.87 0.81 0.79 0.42 0.76 0.79 0.78 0 0.62
.85
Metamyelocytes 0.15 0.18 0.18 0.19 0.26 0.18 0.12 0.05 0.03 0.03

Bands 0.03 0.18 0.08 0.4 0.22 0.12 0.08 0.04 0.02 0.03

Segmented 0.06 0.28 0.07 0.64 0.33 0.49 0.22 0.67 0.74 0.72 0 0.62
.85
Lymphocytes 0.48 0.06 0.16 0.05 0.02 0.07 0.23 0.10 0.16 0 0.38
.15
Blast 0.13 0.03 0.06 0.02 0.02

Myelocyte 0.08 0.12 0.20 0.06 0.06 0.05 0.10 0.07 0.03 0
.02
Promyelocyte 0.05 0.08 0.25 0.09 0.19 0.02 0.01
Coagulation Assay 7/8 Referenc 7/13 Referen 7/15 Referen 7/17
e ce ce range
Range Range
PT 12.0 (sec)
10.3-14.1 12.0 10.3-
14.1

Normal Control 12.3 12.2

Prothrombin 1.0 1.0

Ratio

INR 1.0 1.0

Percent Activity 89.2%

Activated PTT 33.2 27.0-45.4 37.4 27.0-

45.4

Normal Control 36.4 37.5

Fibrinogen level 2.5 g/L 2.0-4.0 5.6mg/ 4-8.5 3.4

dl

D-dimer 1011.0 Up to
g/L 246.4
 Blood 7/8 7/13 7/18 7/22 7/24 7/25 7/27 7/29
Chemistry

K mmol/L 3.7 3.5

Na mmol/L 139 138

ioCa mmol/L 1.22

Creatinine mg/dl 1.1 0.94 0.85 0.79 0.81

SGOT-AST U/L 33.7 18.8 23.4

SGPT-ALT U/L 59.7 43.3 54.7 44.2 43.5 54.9 74.2

Total Bilirubin mg/dl 0.37 0.35

Direct mg/dl 0.07 0.07

Bilirubin

Indirect mg/dl 0.30 0.28

Bilirubin
 Chest X-Ray

7/10/08
 Lungfields are clear
 The heart is top normal in size
 Left costophrenic sulcus is blunted
 Diaphragm and right costophrenic sulcus are intact
 IMPRESSION: consider mild pleural reaction on the left, otherwise,
no significant findings.
 Ultrasound of liver and spleen

7/11/08
 Essentially normal liver and spleen
 Urinalysis 7/18

Color Yellow Yellow

Transparency Slightly turbid Slightly turbid

pH 6.50 7.0

Specific gravity 1.015 1.010

Albumin Negative -

Sugar Negative -

Cells:

RBC 10-15/hpf 8 – 12/hpf

Pus cells 0-2/hpf 0 -1/hpf

Bacteria Few Few

Mucus threads Few

Amorphous urates Few

No dysmorhic RBC seen No dysmorphic RBC seen

 Flow Cytometry

 Comprehensive leukemia Panel

 Bone Marrow:
 A predominant population of aberrant myeloblasts with highly variable
light scatter properties expressing CD45, CD13, CD33 and CD117 is
identified at 79.9% of the white cells. The blast cells show absence of
CD34 surface antigen expression of HLA-DR. The phenotypic finding is
consistent with Acute Promyelocytic Leukemia.
 Interpretation Comment: Correlation with cytogenetic findings for 15,17
translocation is required
 Cell Surface markers:
 Abnormal Cell Population: Aberrant promyelocytes are detected at
79.9% of the isolated cells. The flow cell sample was analyzed utilizing
14 antibodies
CD45 (+) CD14 (-) HLA-DR (-)
CD4 (-) CD19 (-) Kappa (-)
CD5 (-) CD20 (-) Lambda (-)
CD7 (-) CD33 (+)
CD10 (-) CD34 (-)
CD13 (+) CD117 (+)
 2D ECHO

7/14/08
 Concentric LVH with good wall motion and
contractility and good systolic function
 EF: 77%
 Culture and Sensitivity

Throat Culture – 7/22/08

 E. coli moderate growth

Blood Culture and Sensitivity

 7/20/08 – Left and Right arm: no growth after 24
hours incubation
 7/24/08 – Left and Right arm: no growth after 5
days incubation
THANK YOU.
Bone Marrow Core Biopsy &
Peripheral Blood smears
Bone Marrow Core Biopsy
Bone Marrow Core Biopsy
Bone Marrow Core Biopsy
Bone Marrow Core Biopsy
Marrow biopsy :

- hypercellular

- the abnormal promyelocytes have abundant cytoplasm

with numerous granules

- occasional Auer rods may be identified

- nuclei are convoluted

Aspirate smear
Aspirate smears
Aspirate smears
Aspirate smears
Aspirate smears
Aspirate smears
Aspirate smears
Morphology:

Nuclear size and shape in the abnormal promyelocytes of

hypergranular APL are irregular (kidney-shaped or
bilobed)

Cytoplasm : densely packed cytoplasm, coalescent large

granules that almost totally obscure the nuclear,
cytoplasmic margin

Characteristic cells containing bundles of Auer rods “faggot

cells” are present in most cases.

Myeloblasts with single Auer rods may also be seen.

Acute Promyelocytic Leukemia
M3-AML
Myeloperoxidase :
strongly Positive
reaction product covering the entire cytoplasm

Non-specific esterase reaction : weakly Positive 25% cases

Microgranular (Hypogranular) APL – apparent paucity or

absence of granules, predominantly bilobed nuclear shape.
Hypogranular cytoplasm relates to submicroscopic size of
the azurophilic granules.
Flow cytometry
Flow cytometry
Flow cytometry
Flow cytometry
Flow cytometry
Flow cytometry
Flow cytometry
 Acute Promyelocytic Leukemia

Immunophenotype:
- APL with t(15;17) has a myeloid phenotype
- Flowcytometry : CD33
CD13- heterogenous
CD2 and CD9 – co-expression

Genetics:
- Retinoic acid receptor alpha (RARα) gene on 17q12 fuses
with 15q22 (PML gene) = PML-RARα gene fusion product
{171, 272, 857}
 Acute Myeloid
Leukemia
(FAB-AML-M3)
 Acute Promyelocytic Leukemia

An acute myeloid leukemia in which abnormal promyelocytes

predominate with both hypergranular or typical APL and
microgranular (hypogranular) types exists.

Epidemiology:
Comprises 5-8% of AML
Can occur at any age but patients are predominantly adults in
midlife
 Acute Promyelocytic Leukemia

Clinical Features of APL

- frequently associated with DIC
- Microgranular APL : leukocyte count is very high
with rapid doubling time
 Acute Promyelocytic Leukemia

Postulated Cell of Origin:

- Myeloid stem cell with potential to differentiate to
granulocytic lineage

Prognosis:
- APL has sensitivity to treatment with all trans-retinoic
acid and Anthracine is favorable
 Acute Promyelocytic Leukemia

3 Variants of APL
2. t (11;17) (q23;21)
- morphological differences with predominance of cells with
regular nuclei, many granules, absence of Auer rods,
increased number of pseudo Pelger-Huet cells & strong
MPO activity.
4. t (15;17) (q32;q12)
-predominant population of hypergranular promyelocytes
- minor population of hypogranular promyelocytes
-Auer rods not identified with LM
3. t (11;17) (q13;q21)
Aspirate smears