Hematology ConferenceSlide 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, 6amDate of Interview : 7/08/08, 7amSource & Reliability : Patient 85% reliability
HPI4 weeks PTA:•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
HPI3 weeks PTA: •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
HPI1 week PTA: •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 specialistA D M I S S I O N
Review of Systems
General(-) weight change(-) chills(-) sweats
Skin(-) rashes (-) sores (-) itching (-) dryness (-) color changes (-) changes in hair or nails
Ears(-) hearing difficulties(-) infection
(-) tinnitus (-) discharge Eyes
(-) redness (-) itchiness (-) glaucoma (-) cataracts
Review of Systems
Nose (-) cold
(-) discharges
Throat/Mouth (-) sore throat (-) hoarseness
Neck(+) submandibular mass, left (-) swollen glands(-) stiff neck
Respiratory (-) hemoptysis (-) wheezing
Gastrointestinal (-) melena and hematochezia
(-) diarrhea/constipation (-) jaundice
Cardiac (-) Chest pain (-) Orthopnea (-) Palpitatons
Review of Systems
Vascular (-) claudication (-) varicosities
Genitourinary (-) urinary frequency (-) hematuria (-) dysuria
Musculoskeletal (-) stiffness (-) muscle pain
(-) joint pain
Psychiatric (-) tension (-) anxiety
Neurologic (+) headache
(-) fainting (-) seizures (-) motor or sensory loss
(-) numbness
Past Medical History
Immunizations: Unrecalled immunizationsOperations: (–) Illnesses: 2003 gouty arthritis – relieved by
Allopurinol and ColchicineAllergies: No known allergies to food or
drugsNo medications or vitamins (-) DM, HPN, Hepatitis
Smoker: 24 pack yearAlcohol 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,
benzeneGood family support/relationship, lives with
wife and 5 childrenGood relationship with peers
Personal and Social History
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
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
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 No sensory deficits DTR's ++ No babinski, No nuchal rigidity
5/55/5
5/55/5
Subjective data (+) gum bleeding (+) dizziness (+) weakness (+) easy fatigability (+) fever of 40.8 deg C
Salient Features
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
Neutrophil 0.09 0.06 0.05 0.31 0.13 0.13 0.05 0.12 0.17 0.10
Metamyelocytes
0.5 0.04 0.01 0.05 0.03 0.07 0.02 0.07 0.04
Bands 0.01 0.02 0.01 0.01 0.02
Segmented 0.03 0.02 0.04 0.24 0.1 0.05 0.05 0.09 0.08 0.06
Lymphocytes 0.66 0.31 0.45 0.46 0.66 0.78 0.92 0.54 0.58 0.46
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 7/27 ()
7/27 () 7/29 7/30 7/31 8/1 8/2
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 2.96 3.27
Hct 0.23 0.24 0.29 0.28 0.27 0.27 0.27 0.27 0.25 0.27 0.24 0.27
MCV 81.5 80.8 82.6 82.5 83.4 82.4 84.0 82.82 82.2 82.9 81.7 82.0
MCH 28.1 29.4 28.9 29.4 29.2 29.7 28.9 28.6 28.7 29.1 29.0 29.1
MCHC 34.5 36.4 35.0 35.6 35.0 36.1 34.5 34.6 34.9 35.1 35.5 35.5
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 1.60 2.90
Neutrophil 0.24 0.64 0.33 0.87 0.81 0.79 0.42 0.76 0.79 0.78 0.85 0.62
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 0.85 0.62
Lymphocytes 0.48 0.06 0.16 0.05 0.02 0.07 0.23 0.10 0.16 0.15 0.38
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 Reference Range (sec)
7/13 ReferenceRange
7/15 Reference range
7/17 Reference range
PT 12.0 10.3-14.1 12.0 10.3-14.1
Normal Control 12.3 12.2
Prothrombin Ratio 1.0 1.0
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/dl 4-8.5 3.4
D-dimer 1011.0g/L Up to 246.4
Blood Chemistry 7/8 7/13 7/18 7/22 7/24 7/25 7/27 7/29
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 Bilirubin mg/dl 0.07 0.07
Indirect Bilirubin mg/dl 0.30 0.28
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
7/14/08Concentric LVH with good wall motion and
contractility and good systolic functionEF: 77%
Culture and Sensitivity
Throat Culture – 7/22/08E. coli moderate growth Blood Culture and Sensitivity7/20/08 – Left and Right arm: no growth after
24 hours incubation7/24/08 – 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 LeukemiaM3-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 AMLCan 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 APL1.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.
2.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