CLINICAL PATHOLOGY
CASE 1
CASE SUMMARY
HISTORY
• Age: 5 years
• Sex: male
SIGNS AND SYMPTOMS
• Nasal congestion
• Cough
• Constant headache
• Osteodynia
• Easy bruising
PHYSICAL EXAMINATION
• Swollen lymph nodes
Region: axillary, cervical and submandibullar region
• Splenomegaly
• Hepatomegaly
• Hematoma
Region: trunks and limbs
DIFFERENTIAL DIAGNOSIS
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Hairy Cell Leukemia
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Tuberculosis
Malaria
HAIRY CELL LEUKEMIA
RULE IN
RULE OUT
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Splenomegaly
swollen lymph node
bruising
osteodynia
hepatomegaly
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Other symptoms does not
match
Histology section depicts
otherwise
There is no detailed history
of patient
Age doesn’t meet the
range ( 55 years)
ACUTE MYELOID LEUKEMIA
Rule in
Rule Out
Easy bruising
Histology finding depicts
otherwise
Headache
Hepatomegaly
splenomegaly
Does not fall under the
average age (patient is 5
years of age)
osteodynia
ACUTE LYMPHOBLASTIC LEUKEMIA
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Rule in
Common in young children
Constant headache
Osteodynia
Easy bruising
Splenomegaly
Hepatomegaly
Swollen lymph node
Cough
Nasal congestion
Rule out
 No detailed history of
patient.
TUBERCULOSIS
RULE IN
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Cough
Hepatosplenomegaly
Erythema nodosum
Lymphadenopathy
RULE OUT
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Not enough patient history is
taken
Other symptoms do not match
Age
MALARIA
Rule In
Rule Out
Age group
Malaria caused by
mosquitoes
Dry cough
Mostly affects RBC
Hepatosplenomegaly
Doesn’t affect much in
lymphocyte, monocyte
increases.
Other symptoms common
MAIN DIAGNOSIS
ACUTE LYMPHOBLASTIC
LEUKEMIA
• Acute Lymphoblastic Leukemia is a type of cancer
whereby too many immature lymphocytes are
made by the bone marrow.
• It is a cancer affecting white blood cells and bone
marrow. The affected cells at this case are
lymphocytes thus giving the name lymphoblastic.
• ALL has been rated as one of the most common
cancer disease in children younger than 15 years.
RISK FACTORS
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Exposure to benzene and radiation
Conditions caused by genetic factors
Viruses
Overweight or obesity
Weakened immune system
SIGNS AND SYMPTOMS
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Fever
Cough
Easy bruising
Headache
Swollen lymph nodes
Sweating
Bone pain
Weight loss
Fatigue
Petechiae
Splenomegaly
Hepatomegaly
Hematoma
CONFIRMATION OF DIAGNOSIS
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Physical and Abdominal Examination
Complete blood count
Peripheral blood smear
Blood chemistry and coagulation test
Bone marrow Tests: Aspiration and Biopsy
Cytochemistry
Flow cytometry
immunohistochemistry
• Cytogenetics
• Fluorescent in situ hybridization (FISH)
• Polymerase Chain Reaction (PCR)
• Lumbar puncture
• Lymph node biopsy
Imaging Tests:
• Computed Tomography Scan
• Magnetic Resonance Imaging Scan
• X Rays
• Ultrasound
• Bone Scan
DISCUSSION
WHY ACUTE LYMPHOBLASTIC
LEUKEMIA ?
• ALL has been chosen as the confirmed diagnosis of
the case because mainly all the symptoms , and
histological findings match those of Acute
Lymphoblastic Leukemia.
• Age is also one of the factors which rules in for the
diagnosis
Five year old boy
• Acute lymphoblastic leukemia happens in the age
group of people younger than 15 years, thus age has
been chosen as a factor to rule in for the diagnosis.
• Nasal congestion- membrane lining in the nose
becomes swollen from inflamed blood vessels.
• Cough- can be due to enlarged thymus.
• Constant headache- shortages of normal blood cells,
and can be due to if ALL is spread to the brain by lymph
nodes.
• Osteodynia- aka bone pain, caused by the spread of
blasts cells to the surface of the bone or into the point
from the marrow cavity.
• Easy bruising- shortages of normal blood cells. Also by
blood vessels under the skin being damaged. Platelet
levels are low.
• Swollen lymph nodes – Lymphoblasts build up in the bone
marrow and may spread to other sites in body.
Accumulation of leukemia cells
• Splenomegaly/Hepatomegaly- accumulation of leukemia
cells. Also by pressure on splenic veins.
• Hematoma- can be presented as lumps which is caused by
the limitation of the blood to a sac
Region: trunks and limbs
• Weight loss- Abdominal pain, so the patient doesn’t have
desire to eat, therefore weight decreases.
• Sweating- can be due to body trying to fight the disease.
• Petechiae- are tiny red spots or lines in the skin due to low
platelet levels.
The histological slide shows lymphocytes that has scant agranular
cytoplasm, small nucleoli and condensed nuclear chromatin which matches
to be distinctive histologic features of lymphocyte in acute lymphoblastic
leukemia
MANAGEMENT
• Stem Cell Transplant
• Chemotherapy: 3 phases
-Induction
-Consolidation
-Maintenance
PROGNOSIS
• Mean survival rate: 5 year –90%
REFERENCES
• De Kouchkovsky, I. and Abdul-Hay, M. (2016). ‘Acute myeloid
leukemia: a comprehensive review and 2016 update’. Blood Cancer
Journal, 6(7), pp.e441-e441.
• Kotepui, M., Phunphuech, B., Phiwklam, N., Chupeerach, C. and
Duangmano, S. (2014). Effect of malarial infection on
haematological parameters in population near Thailand-Myanmar
border. Malaria Journal, 13(1), p.218.
• Kumar.V;Abbas. A; Aster.J: RobbinandCotrans: Pathologic Basis of
Disease, 9th edition, Elsevier Saunders, (2015), pg 592– 604
• Lowenberg, B. and Rowe, J. (2015). Introduction to the review
series on advances in acute myeloid leukemia (AML). Blood, 127(1),
pp.1-1.
• Marais, B. (2014). Tuberculosis in children. Journal of Paediatrics
and Child Health, 50(10), pp.759-767.
• Ramesh, V., Venkata, N. and Sankar, J. (2017). Mixed malarial
infection with pancytopenia in a child with acute lymphoblastic
leukemia: An unusual presentation. Indian Journal of Medical and
Paediatric Oncology, 38(1), p.92.
• Saultz, J. and Garzon, R. (2016). Acute Myeloid
Leukemia: A Concise Review. Journal of Clinical
Medicine, 5(3), p.33.
• Terwilliger, T. and Abdul-Hay, M. (2017). Acute
lymphoblastic leukemia: a comprehensive review and
2017 update. Blood Cancer Journal, 7(6), p.e577.
• Torpy, J. (2014). Acute Lymphoblastic Leukemia. JAMA,
301(4), p.452.
• Troussard, X. and Cornet, E. (2017). Hairy cell leukemia
2018: Update on diagnosis, risk-stratification, and
treatment. American Journal of Hematology, 92(12),
pp.1382-1390.
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MANAGEMENT
-STEM CELL TRANSPLANT
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-CHEMOTHERAPY
usually in 3 phases:
Induction
Consolidation
Maintenance
Induction treatment
• SR/IR induction: Prednisolone tablets
• HR induction : dexamethasone
• Vincristine: IV weekly
• doxorubicin: 2 doses IV on the 1st and 22nd day.
• PEG-asparaginase: 1 dose of IM towards the finishing of induction treatment.
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High risk
Block A
Day 1: triple intrathecal
Day 1-5 : cyclophosphamide 440 mg/m2
etoposide 100 mg/m2
Day 6: PEG asparaginase
Block B
dexamethasone + mercaptopurine: orally,
day 3 and 8: vincristine
day 3: 5 g-MTX
day 7 and 8:2 doses of cytarabine 2 g/m2
day 4: triple intrathecal
day 8: PEG asparaginase
Block C
Day 1: triple intrathecal
Day 2 and 6:fludarabine 30 mg/m²
cytarabine 2g/m² days
Day 2 and 4 :idarubicin 8 mg/m²
Day 7: PEG-asparaginase
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Consolidation
Standard and intermediate risk
Mercaptopurine tablets: oral
vincristine: 2 doses IV
PEG asparaginase: 4 doses at a fortnightly interval
With all high-dose methotrexate courses,
Intrathecal methotrexate is given
Delayed intensity
Standard and intermediate risk
• Dexamethasone tablets orally during 1st and 3rd week with a break
during the 2nd week and a taper during the 4th week.
• methotrexate: 2 doses intrathecal
• vincristine: 4 injections weekly
• PEG asparaginase injection: IM every second week ( 4 times)
• Daunorubicin: infusion weekly (4 times)
• Cyclophosphamide 1 g/m2 starting on 4th week. 6 thioguanine
tablets given by oral administration.
• Low dose cytarabine injections daily x 4 days during 4th and 5th
week
• Thioguanine : for 2 weeks from week 4 given orally on a daily basis.
Maintenance
• If leukemia remains in remission after induction and consolidation phase,
maintenance therapy can begin.
• Most treatment plans use daily 6- mercaptopurine and weekly methotrexate,
given as pills, along with vincristine which is given intravenously and a steroid,
usually prednisone or dexamethasone. Other drugs may be added depending on
the type of ALL and risk of reoccurring. Treatment plans during the first few
months of maintenance phase include one or two repeat intensified treatments
which is similar to the initial induction. These four weeks of intensifications are
often called re- induction or delayed intensification.
• The total length of therapy (induction, consolidation and maintenance) for Acute
Lymphoblastic Leukemia treatment plans is two to three years.
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Treatment plans may change if leukemia does not go into remission during
induction and consolidation phase. Child’s bone marrow may be checked properly
soon after the treatment starts to observe if the leukemia is going away. If not,
treatment may be intense and prolonged.