HEMATOLOGY

and ONCOLOGY

Ma. Catherine G. Dones, MD, DPPS

 Yu Na-bi , aged 2 years, was What would be your primary consideration?
noted to look pale when she went a. B thalassemia
to the clinic for a well baby
b. Iron deficiency anemia
consult. CBC revealed hgb of
5g/dL, MCV 54 (normal 72-85) and c. Alpha thalassemia trait
MCH 16 (normal 24-39). She was d. Anemia of chronic disease
drinking 3 pints of cow’s milk per
day and was a picky eater,
refusing meat. No pertinent past
medical history elicited.
 Yu Na-bi , aged 2 years, was What would be your primary consideration?
noted to look pale when she went a. B thalassemia
to the clinic for a well baby
b. Iron deficiency anemia
consult. CBC revealed hgb of
5g/dL, MCV 54 (normal 72-85) and c. Alpha thalassemia trait
MCH 16 (normal 24-39). She was d. Anemia of chronic disease
drinking 3 pints of cow’s milk per
day and was a picky eater,
refusing meat. No pertinent past
medical history elicited.
 ETIOLOGY
Iron Deficiency INFANTS AND
TODDLERS
OLDER CHILDREN &
ADOLESCENTS

Anemia - Low birth weight

infants
- Increased
requirements
- Prematurity (growth spurt)
-ANEMIA OF INADEQUATE - Perinatal blood loss
- Early cord clamping
- Occult/chronic
blood loss
PRODUCTION - Excessive - Menstrual blood
consumption of loss
- insufficient total body iron to cow’s milk - Infection
(hookworm, giardia,
maintain normal physiologic H pylori)
functions
- most common nutritional
deficiency in children
 Diagnostics
CBC - Low RBC, MCV, retic count

Iron Deficiency - Increased red cell distribution width (vs

Thalassemia, normal RDW)

Anemia PBS - Microcytic, hypochromic RBCs (from

decreased hgb production or faulty function)
Others - Low serum iron and ferritin
Manifestations - High total iron binding capacity (vs anemia of
chronic disease- low Fe, TIBC)
- Mild to moderate: asymptomatic
- Hgb 6-10g/dL : Mild irritability
- Hgb 7-8g/dL: pallor (most impt clinical sign)
- Hgb <5g/dL: lethargy, anorexia, easy
fatigability, systolic flow murmurs, high output
cardiac failure
- KOILONYCHIA: spoon nails
- PICA: desire to eat non- nutritive substances
- PAGOPHAGIA: desire to ingest ice
 RESPONSE to FE
Iron Deficiency TIME
12-24 hours
RESPONSE
Subjective improvement

Anemia 36-48 hours

(less irritability)
Initial bone marrow
response (erythroid
hyperplasia)
Management 48-72 hours reticulocytosis
General - Address any underlying cause 4-30 days Increase in Hgb
- Dietary counselling: cow’s milk >1yo only, with
1-3 months Repletion of iron stores
limit of 24 oz/day
Iron - Fe salts: 4-6mkd of elemental Fe
- Elemental Fe: Ferrous sulfate with 20%, FOLLOWUP
Ferrous fumarate 33%, ferrous gluconate 12% - repeat CBC 4 wks after Fe
- Continue up to 2-3 mos after Hgb normalized - For severe anemia, check for reticulocytosis
BT - For imminent heart failure or severe anemia in 2-3 days
from blood loss - If poor response, consider other causes
 ACQUIRED ETIOLOGY

Aplastic Anemia Cytotoxic

drugs and
radiation
• Chemotherapy
• radiation

-ANEMIA OF INADEQUATE Drug/chemical

reaction
•
•
Antiseizure (carbamazepine, phenytoin)
Antibiotics (chloramphenicol)
PRODUCTION • NSAIDs (indomethacin)
- life threatening bone marrow • Anti-thyroid (methimazole,
propylthiouracyl)
failure • Other: gold, arsenicals, benzene
HM: peripheral pancytopenia Viral infections • EBV, HIV, Herpes virus
with marrow hypoplasia or Immune • SLE
aplasia disorders • Graft vs host disease
- inherited or acquired Others • Anorexia nervosa
• thymoma
 Aplastic
Manifestations • Recurrent infection due to leukopenia
• Mucosal hemorrhage or menorrhagia due to
thrombocytopenia

Anemia
• Pallor and easy fatiguability due to anemia

Severity of Aplastic Anemia

MODERATE SEVERE
APLASTIC ANEMIA APLASTIC ANEMIA
ANC: WBC x neutrophils Absolute Neutrophil 500-1000/mm3 <500/mm3
100 count (ANC)
Platelet count 20,000- <20,000/mm3
100,000/mm3
Corrected retic= %retic count x patient’s Hct Corrected <1% <1%
45 (normal Hct) reticulocyte count
 Diagnostics • CBC and PBS: pancytopenia (anemia,

Aplastic
leukopenia and thrombocytopenia)
• BMA: establish the diagnosis, hypocellular
marrow with decrease in all cell components

Anemia Management • Treatment of choice: Allogenic hematopoietic

stem cell transplant
• Immunosuppressive therapy (treatment if with
no HLA match)
• RBC and platelet transfusion
• GCSF /granulocyte colony stimulating factor
• GMCSF/ granulocyte-macrophage colony
stimulating factor
• Withdrawal of toxic agent
 ETIOPATHOGENESIS DIAGNOSIS MANAGEMENT
FANCONI ANEMIA

Congenital ü Most common

inherited aplastic
anemia
Based on cytogenetic
analysis
•

•
Allogenic hematopoietic
BM transplant
Androgen improve blood

Aplastic ü Cells cannot repair

DNA damage/
interstrand crosslinks
•
counts
BT, GCSF

Anemia SHWACHMAN- DIAMOND SYNDROME

ü Autosomal recessive Based on BM dysfunction • Oral pancreatic
ü Genetic mutation and exocrine pancreatic enzyme replacement
affecting ribosome dysfunction • Fat-soluble vitamins
synthesis • BT, GCSF
• Stem cell transplant
DIAMOND –BLACKFAN SYNDROME
ü >90% diagnosed All should be met: • Steroids
within 1yo o Age <1yo • BT if steroids are not
ü Mutation affecting o Macrocytic anemia, tolerated
ribosome synthesis no other cytopenia
o Reticulocytopenia
o Normal marrow
cellularity
 On a routine screening complete The child is most likely to have
blood count, a 2 year old is noted a. Iron deficiency anemia
to have microcytic anemia. A
b. B- thalassemia trait
follow up hemoglobin
electrophoresis demonstrates an c. Sickle cell anemia
increased concentration of d. Chronic systemic illness
hemoglobin A2. e. Lead poisoning
 On a routine screening complete The child is most likely to have
blood count, a 2 year old is noted a. Iron deficiency
to have microcytic anemia. A
b. B- thalassemia trait
follow up hemoglobin
electrophoresis demonstrates an c. Sickle cell anemia
increased concentration of d. Chronic systemic illness
hemoglobin A2. e. Lead poisoning
Thalassemia
ALPHA BETA
THALASSEMIA THALASSEMIA

- alpha and globin chains are Cause Gene deletions

in one or more
Mutations in one
or both of the beta
disrupted due to disease- genes encoding globin genes
causing variant in one or more for alpha globin
globin genes chain

- HEMOLYTIC ANEMIA
Thalassemia
ALPHA THALASSEMIA BETA THALASSEMIA
TYPES Hydrops fetalis • 4 foci deleted B thalassemia • Both beta globin genes
with Barts Hgb • Severe microcytic anemia major mutated
• Severe microcytic anemia
with target cells
• Transfusion dependent
Thalassemia • 3 foci deleted B thalassemia • At least 1 beta globin genes
major (HbH • Moderate microcytic intermedia mutated
disease) anemia • Moderate microcytic
anemia
• Non-transfusion dependent
Thalassemia • 2 foci deleted B thalassemia • One beta globin gene
minor • Mild microcytic anemia minor/ trait mutated
• Carrier
Silent carrier • 1 foci deleted • Mild microcytic anemia
• Normal, hemoglobin,
normal MCV
Thalassemia
ALPHA THALASSEMIA BETA THALASSEMIA
Diagnostics • definitive: hemoglobin electrophoresis
• CBC
- anemia and low red cell indices with normal red cell distribution width
- decreased reticulocyte count due to ineffective erythropoiesis
• PBS: microcytic, hypochromic RBCs, target cells and Heinz bodies
Management • Hematopoietic stem cell transplantation (4 foci deletion, Beta
thalassemia major)
• BT, iron chelation with deferoxamine or deferasirox
• Splenectomy (for hypersplenism)
A 2 year old boy presents to the Which of the following is the most likely
clinic for an ear check. The child diagnosis?
had an ear infection that was a. Iron deficiency anemia
treated with co-trimoxazole 3 wks b. Megaloblastic anemia
earlier. On PE, patient is noted to
c. Glucose-6-phosphate dehydrogenase
be extremely pale. Hemoglobin
deficiency
and hematocrit were obtained and
are noted to be 7g/dL and 22%
respectively.
A 2 ear old boy presents to the Which of the following is the most likely
clinic for an ear check. The child diagnosis?
had an ear infection that was a. Iron deficiency anemia
treated with co-trimoxazole 3 wks b. Megaloblastic anemia
earlier. On PE, patient is noted to
c. Glucose-6-phosphate dehydrogenase
be extremely pale. Hemoglobin
deficiency
and hematocrit were obtained and
are noted to be 7g/dL and 22%
respectively.
 PRECIPITANTS OF HEMOLYSIS
DRUGS
• Antibacterial: nitrofurantoin, furazolidone, nitrofurazone

Glucose-6- • Analgesics: aspirin

• Antihelminthics: B-naphthol, niridazole, stibophan
• Antimalarials: chloroquine, primaquine, pentaquine

phosphate • Sulfonamides: cotrimoxazole, sulfonylureas

• Others: dimercaprol, isobutyl nitrate, probenecid
CHEMICALS

dehydrogenase • Methylene blue

• Phenylhydrazine
• Toluidine blue

deficiency • Aniline dye

FOOD and DRINKS
• Fave beans
• Red wine
• Legumes
• Blueberry
- most common inherited enzymatic • Soya
disorder OTHERS:
- genetic defect in RBC G6PD • Menthol
• Camphor
- causes HEMOLYTIC ANEMIA when • Naphthalene (moth balls)
exposed to oxidative stress • Henna
 Manifestations Most are asymptomatic unless triggered
Glucose-6- Hemolysis in 24-48 hours after exposure

phosphate Diagnostics G6PD assay

CBC with PBS: low Hgb, Heinz bodies,
anisopoikilocytosis, bite cells
dehydrogenase Management Avoid triggers

deficiency Acute hemolytic episode: identify and

remove culprit, hydrate and transfuse
for severe anemia
 A 7 year old diagnosed last year Which of the following is an appropriate
with sickle cell disease after a measure for this patient?
pain crisis comes to the clinic for
a routine checkup. He has been a. Monthly RBC transfusion
well on hydroxyurea with no pain
b. Pneumococcal vaccine
crises or acute chest episodes
since starting the medication a c. Splenectomy
year ago. He has had no infections d. Treatment with deferoxamine
over the last year and today has e. Weekly intramuscular benzathine
no fevers or evidence of penicillin
increasing splenomegaly.
 A 7 year old diagnosed last year Which of the following is an appropriate
with sickle cell disease after a measure for this patient?
pain crisis comes to the clinic for
a routine checkup. He has been a. Monthly RBC transfusion
well on hydroxyurea with no pain
b. Pneumococcal vaccine
crises or acute chest episodes
since starting the medication a c. Splenectomy
year ago. He has had no infections d. Treatment with deferoxamine
over the last year and today has e. Weekly intramuscular benzathine
no fevers or evidence of penicillin
increasing splenomegaly.
 Pathogenesis • Autosomal recessive
• Develops in 6 mos of age when sickle cell
Hgb replaces HbF

Sickle Cell Manifestation • Hallmarks: vasoocclusive phenomena and

hemolysis

Disease •

•
Recurrent painful episodes from hypoxic
tissue injury
Organ system complications: aplastic
crisis, splenic sequestration, priapism,
stroke, avascular necrosis, acute chest
syndrome

- HEMOLYTIC ANEMIA • High performance liquid chromatography

Diagnosis
• Hgb electrophoresis
• PBS: Howell Jolly bodies, sickle cells
• “Crew cut” or “hair on end” -Skull xray

Management Analgesics, hydration for acute crises

Hydroxyurea – promote production of fetal
hemoglobin
Vaccination
Folate supplement
A preterm infant was found to be Which of the following would be one of
jaundiced 12 hours after birth. At 36 your considerations?
hours of age, the serum bilirubin was
a. Pyruvate kinase deficiency
18mg/dL, hemoglobin was 12.5mg/dL
and reticulocyte count 95. Many b. Hereditary spherocytosis
nucleated red cells and some c. Sickle cell anemia
spherocytes were seen in the d. Rh incompatibility
peripheral blood smear.
e. Polycythemia
A preterm infant was found to be Which of the following would be one of
jaundiced 12 hours after birth. At 36 your considerations?
hours of age, the serum bilirubin was
a. Pyruvate kinase deficiency
18mg/dL, hemoglobin was 12.5mg/dL
and reticulocyte count 95. Many b. Hereditary spherocytosis
nucleated red cells and some c. Sickle cell anemia
spherocytes were seen in the d. Rh incompatibility
peripheral blood smear.
e. Polycythemia
 Pathogenesis Due of abnormalities of ankyrin and spectrin
(proteins in RBC cytoskeleton)

Hereditary Manifestations Pallor, jaundice

Splenomegaly
Susceptible to aplastic crisis (Parvo B19)

Spherocytosis Diagnosis Osmotic fragility test: (+) fragile sphere

shaped rbc
CBC: high MCHC, normal MCV, high retic
count
- HEMOLYTIC ANEMIA PBS: spherocytes
Increase indirect bilirubin
- Most common cause of
Management Splenectomy for:
hemolytic anemia due to red cell • Transfusion-dependent
membrane defect • Severe disease
• Moderate disease with hypoplastic or
aplastic crises, poor growth, cardiomegaly
• Folate supplement
Common Findings
Among Bleeding
Disorders
Common ITP
PT
Normal
PTT
normal
BT
prolonged
Platelet
decreased
Findings Hemophilia
vWD
normal
normal
prolonged
prolonged
normal
prolonged
normal
Normal/
Among DIC prolonged prolonged prolonged
decreased
decreased

Bleeding Vit K
deficiency
prolonged Prolonged
or normal
normal Normal

Disorders
Two weeks after a viral syndrome, What is the most likely diagnosis?
a 2 year old child develops a. Von Willebrand disease
bruising and generalized
b. Acute Leukemia
petechiae, more prominent over
the legs. No hepatosplenomegaly c. Idiopathic thrombocytopenic purpura
or lymph node enlargement is d. Aplastic anemia
noted. The examination is e. Thrombotic thrombocytopenic purpura
otherwise unremarkable.
Laboratory testing shows the
patient to have a normal
hemoglobin, hematocrit and WBC
and differential. The platelet
count is 15k.
Two weeks after a viral syndrome, What is the most likely diagnosis?
a 2 year old child develops a. Von Willebrand disease
bruising and generalized
b. Acute Leukemia
petechiae, more prominent over
the legs. No hepatosplenomegaly c. Idiopathic thrombocytopenic purpura
or lymph node enlargement is d. Aplastic anemia
noted. The examination is e. Thrombotic thrombocytopenic purpura
otherwise unremarkable.
Laboratory testing shows the
patient to have a normal
hemoglobin, hematocrit and WBC
and differential. The platelet
count is 15k.
 Etiology Triggered by viral infections, immunologic,
environmental factors

ITP Manifestation • Previously healthy with sudden generalized

petechiae and purpura
• Recent viral illness
IMMUNE/ IDIOPATHIC BLEEDING SEVERITY:
• MILD: bruising, petechiae

THROMBOCYTOPENIC • MODERATE: more severe skin and mucosal

lesions, epistaxis, menorrhagia
• SEVERE: bleeding requiring BT
PURPURA Diagnostics CBC: platelet <20K, normal Hgb/ WBC
PBS: large platelets
BMA: for those with abnormal WBC and
- most common cause of unexplained anemia
• Normal/increased megakaryocytes
thrombocytopenia in kids • Normal erythroid & myeloid precursor
- immune-mediated Management None – mild/moderate
IVIg: 0.8-1g/kg
- peak: 1-4 yo Prednisone: 1-4mg/kg/day
Splenectomy for: intracranial bleed, kids>4yo
with chronic ITP lasting for>1yr, sx difficult to
control
TTP Etiology Thrombotic microangiopathy from reduced
activity of vWfactor-cleaving protease ADAMTS13
THROMBOTIC Manifestation • Platelet rich thrombi in small vessels ⇢
hemolytic anemia and thrombocytopenia
THROMBOCYTOPENIC • FAT RN
• Fever

PURPURA • Anemia
• Thrombocytopenia
• Renal dysfunction
• Nervous system changes (sz, disoriented)
Diagnostics Microangiopathic hemolytic anemia
(schistocytes, Spherocytes, helmet cells)
Elevated reticulocyte count
Thrombocytopenia
Elevated BUN, Crea
Management Plasmapheresis to reverse platelet consumption
Rituximab, steroid and splenectomy for refractory
cases
A 17 year old boy with a history of Which of the following should this patient
mild hemophilia A presents to the ER receive prior to undergoing an appendectomy
with right lower quadrant pain. to reduce the risk of hemorrhage?
Yesterday, the patient developed
periumbilical abdominal pain,
nausea, vomiting and anorexia. This a. Aspirin
morning, the pain radiated to the b. Desmopressin
right lower quadrant. On PE, the
c. Packed RBCs
patient has positive psoas and
obturator signs. An ultrasound d. Platelets
revealed nonperforated appendix was e. Whole blood
noncompressible with wall thickness
of 5mm. Acute appendicitis was
considered. Patient’s coagulation
factor VIII is slightly lower than
normal.
A 17 year old boy with a history of Which of the following should this patient
mild hemophilia A presents to the ER receive prior to undergoing an appendectomy
with right lower quadrant pain. to reduce the risk of hemorrhage?
Yesterday, the patient developed
periumbilical abdominal pain,
nausea, vomiting and anorexia. This a. Aspirin
morning, the pain radiated to the b. Desmopressin
right lower quadrant. On PE, the
c. Packed RBCs
patient has positive psoas and
obturator signs. An ultrasound d. Platelets
revealed nonperforated appendix was e. Whole blood
noncompressible with wall thickness
of 5mm. Acute appendicitis was
considered. Patient’s coagulation
factor VIII is slightly lower than
normal.
Hemophilia
HEMOPHILIA HEMOPHILIA HEMOPHILIA
A B C

- hereditary, sex-linked, almost TYPES Factor VIII Factor IX Factor XI

deficiency deficiency deficiency

exclusive in males inheritance X linked X linked Autosomal

recessive recessive recessive
- delayed clotting of blood due to
deficiency in clotting factors Most common
Most severe
Hemophilia
HEMOPHILIA A HEMOPHILIA B HEMOPHILIA C

Manifestations • First sign of early joint hemorrhage: warm, tingling sensation in the
joint
• Easy bruising
• Hallmark: hemarthrosis
• Most common earliest joint involved: ankle
• Older children and adolescents: knees and elbows
• Intramuscular hematoma

Diagnostics • Bleeding time: Normal

• Prothrombin Time and INR: Normal
• Prolonged PTT
• Decreased Factor levels

Management Factor VIII Factor IX Factor XI

Cryprecipitate, FFP, Cryosupernate Cryosupernate
Emicizumab FFP FFP
Desmopressin
An 8 year old boy presents to his A workup for von Willebrand’s disease would
pediatrician with recent onset of most likely reveal which of the following?
daily nosebleeds that have been
occurring over the past 2 weeks. a. Increased bleeding time
He has bruises on his legs and
b. Normal coagulation factor concentration
arms that appeared after playing
on the playground at school. The c. Prolonged prothrombin time
patient has a history of easy d. Shortened partial thromboplastin time
bruising since early childhood. He e. Thrombocytopenia
denies painful, tender, or swollen
joints. The boy’s mother reports
that she has history of von
Willebrand’s disease.
An 8 year old boy presents to his A workup for von Willebrand’s disease would
pediatrician with recent onset of most likely reveal which of the following?
daily nosebleeds that have been
occurring over the past 2 weeks. a. Increased bleeding time
He has bruises on his legs and
b. Normal coagulation factor concentration
arms that appeared after playing
on the playground at school. The c. Prolonged prothrombin time
patient has a history of easy d. Shortened partial thromboplastin time
bruising since early childhood. He e. Thrombocytopenia
denies painful, tender, or swollen
joints. The boy’s mother reports
that she has history of von
Willebrand’s disease.
Von Pathogenesis •
•
Most common inherited bleeding disorder
Missing or defective von Willebrand factor

Willebrand’s
• Type 1 or 3 – quantitative defect in vWF
• Type 2 – qualitative defect in vWF
• Autosomal dominant

disease Manifestations •
•
Disturbs primary and secondary hemostasis
Increase bleeding time ⇢ membranous membrane
bleeding, petechiae, purpura
• With family history

Diagnostics ü Decreased vWF

ü Decreased factor VIII
ü Prolonged bleeding time
ü Abnormal platelet adhesion
ü Increased PTT
ü Ristocetin cofactor assay

Management DESMOPRESSIN – increase circulating vWF

Antifibrinolytics
A 2 year old child in shock has Clotting studies are likely to show which of
multiple nonblanching purple lesions the following?
of various sizes scattered about in
a. Increased levels of factors V and VIII
the trunk and extremities; petechiae
are noted, and blood oozing from the b. A decrease prothrombin level
puncture site has been observed. c. An increased fibrinogen level
The child’s peripheral blood is d. Presence of fibrin split products
presented.
e. Normal partial thromboplastin time
(PTT)
A 2 year old child in shock has Clotting studies are likely to show which of
multiple nonblanching purple lesions the following?
of various sizes scattered about in
a. Increased levels of factor V and VIII
the trunk and extremities; petechiae
are noted, and blood oozing from the b. A decrease prothrombin level
puncture site has been observed. c. An increased fibrinogen level
The child’s peripheral blood is d. Presence of fibrin split products
presented.
e. Normal partial thromboplastin time
(PTT)
 Pathogenesis Tissue factor activation of coagulation system

DIC
Primary mediator: interleukin 6⇢ thrombin generation, intravascular
fibrin deposition and platelet consumption⇢ destruction of fibrin,
fibrinogen and clotting factors V And VIII

Manifestations • Diffuse bleeding tendency (hematuria, melena, purpura,

petechiae, persistent oozing from needle punctures)
• Circulatory collapse, poor skin perfusion, early ischemic changes
• Thrombotic lesions (major vessel thrombosis, gangrene, purpura
fulminans)

Diagnosis Prolonged PT and PTT

Decreased platelet count and fibrinogen
Elevated fibrin-fibrinogen split products and D –dimer

Management Identify and manage underlying cause

Blood transfusion: FFP for coagulation factors, Cryoprecipitate for
fibrinogen and factor VIII, Platelet concentrate for platelet
ONCOLOGY
An 8 year old boy is brought to the What is the next step in the patient’s
clinic due to refusal to walk for 3 management?
days. On questioning, he states that
both his legs hurt. His mother states
that he has not been himself for the a. Bone marrow biopsy
past month or so and has been b. Delivery of emergent chemotherapy
sleeping much more than usual. She
c. Platelet transfusion
has attributed this to her assumption
that the boy is about to have a growth d. Typing of his brother’s bone marrow to
spurt. On PE, temp is 38.4C, HR 164, assess the potential for a matched related
RR 42, and BP 90/60. The child is pale bone marrow transplant
and listless. Severe hepatomegaly is e. Xray of the chest
noted. No obvious deformities on
legs. Labs: WBC 98, Hgb 8.9, Plt 75,
Na 135, K 4.
An 8 year old boy is brought to the What is the next step in the patient’s
clinic due to refusal to walk for 3 management?
days. On questioning, he states that
both his legs hurt. His mother states
that he has not been himself for the a. Bone marrow biopsy
past month or so and has been b. Delivery of emergent chemotherapy
sleeping much more than usual. She
c. Platelet transfusion
has attributed this to her assumption
that the boy is about to have a growth d. Typing of his brother’s bone marrow to
spurt. On PE, temp is 38.4C, HR 164, assess the potential for a matched related
RR 42, and BP 90/60. The child is pale bone marrow transplant
and listless. Severe hepatomegaly is e. Xray of the chest
noted. No obvious deformities on
legs. Labs: WBC 98, Hgb 8.9, Plt 75,
Na 135, K 4.
 The family of a child just a. Presence of a mediastinal mass
diagnosed with acute b. Hyperdiploidy with more than 50
lymphoblastic leukemia asks for chromosomes
information about the child’s c. WBC count at diagnosis of less than
prognosis. Included as a poor 100,000
prognostic sign is which of the
d. Age between 1 and 10 yrs
following?
e. Early pre-B- cell variety of the disease
 The family of a child just a. Presence of a mediastinal mass
diagnosed with acute b. Hyperdiploidy with more than 50
lymphoblastic leukemia asks for chromosomes
information about the child’s c. WBC count at diagnosis of less than
prognosis. Included as a poor 100,000
prognostic sign is which of the
d. Age between 1 and 10 yrs
following?
e. Early pre-B- cell variety of the disease
 Pathogenesis • Malignant proliferation of lymphoblasts

Acute
• 2 to 6 years old, M > F
• Unknown etio
• RISK FACTORS: Down syndrome,
neurofibromatosis type 1, exposure to radiation

Lymphoblastic in utero and in childhood, benzene exposure,

advanced maternal age

Leukemia Manifestations Acute (<4wks of symptoms)

Nonspecific Sx: anorexia, irritability, lethargy
Signs of marrow failure: anemia, bleeding,
purpuric/petechial lesions, low grade fever
Signs of infiltration: bone pain, lymphadenopathy,
hepatosplenomegaly

Diagnostics BMA: >25% of cells homogenous lymphoblasts

CBC: anemia, thrombocytopenia, atypical
lymphocytes, WBC of >100
PBS: (+) blasts
CXR: mediastinal mass
CSF: lymphoblasts
 CRITERIA STANDARD HIGH risk
(NOT FIT STANDARD RISK
CRITERIA)

Acute AGE
WBC at diagnosis
>1yo and <10yo
<50
<1yo and >10yo
>50

Lymphoblastic
IMMUNOPHENOTYPE Pre B cell T cell, mature B
CNS involvement negative positive
Response to Day 7 absence of Day 7 presence of blasts on

Leukemia steroids blasts on PBS PBS

Management • Most impt prognostic factor:

receipt of treatment
• Standard treatment: Chemo for
2-3yrs
• Treatment goals: BMA blast of
<5%, near normal neutrophil and
platelet
 AML CML JMML

Other Pathogenesis More in adolescents Philadelphia

chromosomal
<2yo

translocation t (9;22)
Leukemias Manifestations • Signs of marrow
failure
•
•
Splenomegaly
Initial chronic phase
•
•
Rashes
Lymphadenopathy
• Subcutaneous (3-4yrs) with mild • Splenomegaly
nodules or anemia and • hemorrhage
blueberry muffin thrombocytosis ⇢
lesions accelerated/ blast
• Gingival crisis with course
infiltration similar to acute
• DIC leukemia

Diagnosis >20% of bone High WBC count with Leukocytosis with

marrow cells are myeloid cells at all stages increased monocytes
blast cells of differentiation in PBS Thrombocytopenia
and BM Anemia with
erythroblasts
Myelodysplastic BM
management Chemo Imatinib, dasatinib, Stem cell
Stem cell transplant hydroxyurea transplantation
An otherwise healthy 17 year old Which of the following would be the
complains of swollen glands in his appropriate next step?
neck and groin for the last 6 months
a. Biopsy of node
and an increasing cough over the
previous 2 wks. He also reports some b. Complete blood count and differential
fever, especially at night, and c. Trial of antituberculosis drugs
possibly some weight loss. On d. Chest radiograph
examination, you notice that he has
e. Cat-scratch titers
nontender cervical, supraclavicular,
axillary and inguinal nodes. No
hepatosplenomegaly and otherwise
looks to be fairly healthy.
An otherwise healthy 17 year old Which of the following would be the
complains of swollen glands in his appropriate next step?
neck and groin for the last 6 months
a. Biopsy of node
and an increasing cough over the
previous 2 wks. He also reports some b. Complete blood count and differential
fever, especially at night, and c. Trial of antituberculosis drugs
possibly some weight loss. On d. Chest radiograph
examination, you notice that he has
e. Cat-scratch titers
nontender cervical, supraclavicular,
axillary and inguinal nodes. No
hepatosplenomegaly and otherwise
looks to be fairly healthy.
 Pathogenesis 20-30 yo and >50yo

Hodgkin’s Associated with EBV, CMV, HHV-6

Patho hallmark: Reed-Sternberg cells

Disease
Manifestations Painless lymphadenopathy (cervical, supraclavicular,
axillary, inguinal)
Mediastinal mass
-Most common Fatigue, anorexia, B symptoms (weight loss, fever, night
sweats)
cancer in adolescent Hepatosplenomegaly

and young adults

Diagnosis Imaging (determine extent): CXR, CT, PET scan
Excision biopsy of lymph node: Reed Sternberg cells
Check for organ involvement: CBC, ESR, LDH, Crea, AST,
ALT

Management Chemotherapy
Radiation
 ANN ARBOR STAGING
Hodgkin’s STAGE I One lymph node group involved

Disease STAGE II 2 lymph node groups involved in

same side of diaphragm

STAGE III 2 lymph node groups involved on

both sides of diaphragm OR
extralymphatic involvement

STAGE IV Diffuse extra-lymphatic site

involvement (BM, CNS, liver)
A 6 year old boy presents to his primary Which of the following would be the
care provider with a nonproductive appropriate diagnosis?
cough, and was assessed to have an
upper respiratory tract infection. a. Pneumonia
However, symptoms persist and follow b. TB
up consult was done. He is noted to be
c. Non-Hodgkin’s Lymphoma
wheezing, a diagnosis of Reactive airway
disease was made. He was given an d. Hodgkin’s Lymphoma
inhaled beta 2 agonist. Patient returned
to doctor for the 3rd time, now
complaining of cough and low grade
fever. Patient was diagnosed with clinical
pneumonia, antibiotic prescribed. Few
days later, patient went to the ER in
respiratory distress. A chest xray was
done, revealing a large mediastinal mass
A 6 year old boy presents to his primary Which of the following would be the
care provider with a nonproductive appropriate diagnosis?
cough, and was assessed to have an
upper respiratory tract infection. a. Pneumonia
However, symptoms persist and follow b. TB
up consult was done. He is noted to be
c. Non-Hodgkin’s Lymphoma
wheezing, a diagnosis of Reactive airway
disease was made. He was given an d. Hodgkin’s Lymphoma
inhaled beta 2 agonist. Patient returned
to doctor for the 3rd time, now
complaining of cough and low grade
fever. Patient was diagnosed with clinical
pneumonia, antibiotic prescribed. Few
days later, patient went to the ER in
respiratory distress. A chest xray was
done, revealing a large mediastinal mass
 Pathogenesis 60% of lymphomas in kids
Associated with EBV, HIV
4 major subtypes:
• Lymphoblastic lymphoma
Non-Hodgkin’s • Burkitt lymphoma
• Diffuse large B cell lymphoma
• Anaplastic large B cell lymphoma
Lymphoma AGGRESSIVE
Manifestations
• Rapidly growing mass
• B symptoms: Fever, night sweats, weight loss
INDOLENT
• Slowly growing lymphadenopathy,
hepatomegaly, splenomegaly, cytopenia

Diagnosis Imaging (determine extent): CXR, CT, PET scan

Excision biopsy of lymph node: malignant cells
(NO Reed –Sternberg cells)
Check for organ involvement: CBC, ESR, LDH,
Crea, AST, ALT

Management Radiation (CNS involvement)

Chemotherapy for B symptoms, Stage III and IV
Bone marrow transplant
 ST JUDE STAGING
STAGE I Single extranodal tumor OR
Single nodal involved
Non-Hodgkin’s STAGE II • Single extranodal tumor with regional

Disease node involvement

• At least 2 nodal areas on same side of
diaphragm
• 2 extranodal tumors on same side of
diaphragm
• Primary GI tumor

STAGE III • 2 extranodal tumors on both side of

diaphragm
• At least 2 nodal areas on both sides of
diaphragm
• Intrathoracic tumor
• Extensive intraabdominal disease

STAGE IV CNS or BM involvement

 A 15 year old girl presents to What is the most likely diagnosis?
the outpatient clinic
complaining of progressive pain a. Fibrous dysplasia
around her left knee that has b. Nonossifying fibroma
become intractable. She states
c. Osteoid osteoma
that the pain is worst at night
and does not respond to NSAID. d. Osteomyelitis
On ROS, she states having e. Osteosarcoma
intermittent fever and gradual
weight loss over the past 3
months. On examination, the
left thigh is swollen, tense and
tender. Laboratory results
reveal hemoglobin 12.4, WBC
10.6, platelet 380, ESR 18mm/h
and Alk phosphatase 320U/L.
Xray of the knee is as shown
 A 15 year old girl presents to What is the most likely diagnosis?
the outpatient clinic
complaining of progressive pain a. Fibrous dysplasia
around her left knee that has b. Nonossifying fibroma
become intractable. She states
c. Osteoid osteoma
that the pain is worst at night
and does not respond to NSAID. d. Osteomyelitis
On ROS, she states having e. Osteosarcoma
intermittent fever and gradual
weight loss over the past 3
months. On examination, the
left thigh is swollen, tense and
tender. Laboratory results
reveal hemoglobin 12.4, WBC
10.6, platelet 380, ESR 18mm/h
and Alk phosphatase 320U/L.
Xray of the knee is as shown
 Pathogenesis • Affects metaphysis of long bones
Osteosarcoma Manifestations • Local pain and swelling, limping
• No systemic symptoms
• Site of metastasis: lungs, bones
- MUSCULOSKELETAL
TUMORS Diagnostics Xray: sunburst pattern
- Most common primary Histopath: spindle cell osteoid

malignant bone tumor Management Chemotherapy

Surgery
A 13 year old boy is brought to the Which of the following chromosomal
physician because of swelling and translocations would most likely be found
pain of his right leg. He says he first in the karyotype of this patient?
noticed these symptoms about 3 a. t (8;14)
months ago, but the pain has gotten
b. t (9;22)
much worse over the past few weeks.
An xray film of the leg shows a large c. t (11;14)
lytic lesion with an onion-skin d. t (11;22)
appearance located midway along e. t (14;18)
the femur. Malignancy is suspected
and a karyotype of the biopsies bone f. t (15;17)
tumor cells is ordered.
A 13 year old boy is brought to the Which of the following chromosomal
physician because of swelling and translocations would most likely be found
pain of his right leg. He says he first in the karyotype of this patient?
noticed these symptoms about 3 a. t (8;14)
months ago, but the pain has gotten
b. t (9;22)
much worse over the past few weeks.
An xray film of the leg shows a large c. t (11;14)
lytic lesion with an onion-skin d. t (11;22)
appearance located midway along e. t (14;18)
the femur. Malignancy is suspected
and a karyotype of the biopsies bone f. t (15;17)
tumor cells is ordered.
 Pathogenesis Affects diaphysis of long bones
Ewing’s Manifestations • Local pain and selling, limitation in range

Sarcoma of motion
• Fever, weight loss
• Site of metastasis: lungs and bones
- MUSCULOSKELETAL TUMORS
- Second most common primary Diagnosis Xray: onion-skinning, Codman triangle,
malignant bone tumor permeative or moth-eaten appearance
Histopath: Undifferentiated small round cell
or neural origin

Management Chemotherapy
Radiation
Surgery
A 7 year old is brought to the ER by If the lesion represents a primary
her parents because of concerns that intracranial neoplasm, which of the
she is not growing and not developing following is the most likely diagnosis?
appropriately. The parents say that a. Craniopharyngioma
the patient has cold intolerance, easy
b. Ependymoma
fatiguability and polyuria. A physical
exam is notable for short stature and c. Hemangioblastoma
bilateral papilledema. Thyroid d. Prolactinoma
function tests are notable for low e. Thyrotropinoma
levels of triiodothyronine, thyroxine
and TSH. An MRI shows an enhancing
multilobulated suprasellar mass with
ring calcification in the region of the
sella turcica.
A 7 year old is brought to the ER by If the lesion represents a primary
her parents because of concerns that intracranial neoplasm, which of the
she is not growing and not developing following is the most likely diagnosis?
appropriately. The parents say that a. Craniopharyngioma
the patient has cold intolerance, easy
b. Ependymoma
fatiguability and polyuria. A physical
exam is notable for short stature and c. Hemangioblastoma
bilateral papilledema. Thyroid d. Prolactinoma
function tests are notable for low e. Thyrotropinoma
levels of triiodothyronine, thyroxine
and TSH. An MRI shows an enhancing
multilobulated suprasellar mass with
ring calcification in the region of the
sella turcica.
Craniopharyngioma

Pathogenesis Solid or solid-cystic tumors arising from remnants of Rathke pouch of

pituitary stalk in suprasellar region

Manifestations • Visual defects from compression of optic chiasm

• Endocrine abnormalities: deficiency of GH, TSH, ACTH, ADH

Diagnosis MRI or CT scan

Endocrine studies

Management Surgical resection

Radiotherapy
A 5 year old girl is brought to the ER Which of the ff is the most likely to be seen
with acute onset of projectile on histological exam of tissue from this
vomiting and severe headache. Her patient?
parents report that over the past a. Cells with round, regular, centrally
couple of months her gait has located nuclei surrounded by a
perinuclear halo
become increasingly unstable. Her
b. Prolific vasculature and receding rows of
medical history is negative for nuclei
seizures and signs of meningitis. PE
c. Rod shaped perinuclear inclusions
is notable for truncal ataxia and
papilledema. CT reveals a mass at d. Round calcification
the cerebellar vermis. e. Small cells with high nuclear
cytoplasmic ratios surrounding the
vasculature
A 5 year old girl is brought to the ER Which of the ff is the most likely to be seen
with acute onset of projectile on histological exam of tissue from this
vomiting and severe headache. Her patient?
parents report that over the past a. Cells with round, regular, centrally
couple of months her gait has located nuclei surrounded by a
perinuclear halo
become increasingly unstable. Her
b. Prolific vasculature and receding rows of
medical history is negative for nuclei
seizures and signs of meningitis. PE
c. Rod shaped perinuclear inclusions
is notable for truncal ataxia and
papilledema. CT reveals a mass at d. Round calcification
the cerebellar vermis. e. Small cells with high nuclear
cytoplasmic ratios surrounding the
vasculature
Medulloblastoma
Pathogenesis Second most common posterior fossa tumor of childhood
Most common malignant brain tumor of childhood

Manifestations • Increased intracranial pressure from obstruction of 4th ventricle ⇢ headache,

N/V, altered mental status, hypertension
• Cerebellar dysfunction: gait ataxia, dysmetria, poor balance

Diagnosis MRI of brain and spine

Skeletal survey
CSF cytology
Liver function tests

Management Surgical resection resection

Radiotherapy
Chemotherapy
 ASTROCYTOMA
Other Pathogenesis • Most common: PILOCYTIC ASTROCYTOMA

Brain • Site: cerebellum

• Most common posterior fossa tumor:
CEREBELLAR ASTROCYTOMA
Tumor Manifestations Subacute progressive symptoms: headache,
sz, weakness, memory loss, visual symptoms,
personality changes
Diagnosis MRI
PET scan
Biopsy – CA not amenable to surgery
Management Surgical resection
Radiotherapy and chemotherapy
While bathing her 2 year old son, a The most likely diagnosis for this child is
mother feels a mass in his abdomen.
a. Neuroblastoma
A thorough medical evaluation of the
child reveals aniridia, hypospadias, b. Wilms tumor
horseshoe kidney, and c. Hepatoblastoma
hemihypertrophy. d. Rhabdomyosarcoma
e. Testicular cencer
While bathing her 2 year old son, a The most likely diagnosis for this child is
mother feels a mass in his abdomen.
a. Neuroblastoma
A thorough medical evaluation of the
child reveals aniridia, hypospadias, b. Wilms tumor
horseshoe kidney, and c. Hepatoblastoma
hemihypertrophy. d. Rhabdomyosarcoma
e. Testicular cencer
 Pathogenesis Most common primary malignant renal
Wilm’s tumor tumor in children
Second most common malignant
abdominal tumor in children

Manifestations Painless abdominal enlargement with

flank mass that does not cross the midline
Hematuria
Hypertension

Diagnosis Abdo UTZ, CT or MRI

Electrolytes
Renal function tests
CXR or CT to rule out metastasis

Management Surgery
Chemotherapy
Radiation
Du-sik, a 3 year old boy was Which of the following is the
taken to the clinic by his mother most likely diagnosis?
because he was not eating as
a. Neuroblastoma
well as usual and had a
distended abdomen, Recently, b. Nephroblastoma
he appeared reluctant to walk c. Rhabdomyosarcoma
and sometimes cried when he
was picked up. His grandmother
thought he had lost weight. On
PE, he seemed miserable and
pale. He was noted to have a
large abdominal mass. Vital
signs revealed an elevated BP.
Du-sik, a 3 year old boy was Which of the following is the
taken to the clinic by his mother most likely diagnosis?
because he was not eating as
a. Neuroblastoma
well as usual and had a
distended abdomen. Recently, b. Nephroblastoma
he appeared reluctant to walk c. Rhabdomyosarcoma
and sometimes cried when he
was picked up. His grandmother
thought he had lost weight. On
PE, he seemed miserable and
pale. He was noted to have a
large abdominal mass. Vital
signs revealed an elevated BP.
Neuroblastoma
Pathogenesis Most common extracranial solid tumor in childhood
Third most common pediatric cancer
Median age: 22 months
Manifestations • Abdominal mass crossing the midline
• Abdominal pain
• Proptosis
• Periorbital ecchymoses (RACOON EYES)
• HORNER SYNDROME: unilateral ptosis, myosis, anhidrosis
• Localized back pain, weakness
• Palpable, nontender subcutaneous nodules
• Fever, weight loss
Diagnosis Abdo CT scan
24 hr urine homovanillic acid (HVA) and vanillylmandelic acid (VMA)
BMA: myelophthisic marrow
Management Surgery
Chemotherapy
Radiation
 HEPATOBLASTOMA
Other Pathogenesis • Rare in kids

Abdominal Manifestations
• Age of diagnosis: <1yr
Large asymptomatic abdominal mass

Tumor Abdominal pain, fatigue, fever, weight loss,

vomiting, anorexia
Diagnosis MRI, abdo CT scan, MRI
Liver biopsy
Tumor marker: alpha fetoprotein
Management Surgery
Chemotherapy
Liver transplant
A 15 year old boy presents to his family What tumor marker is elevated in all
physician after noticing a small, hard patients with this lesion?
nodule on testicular self-examination.
The patient denies pain in his testicles or a. Carcinoembryonic antigen
scrotum, or any difficulty or pain b. a-fetoprotein
associated with urination. He denies any
c. B-human chorionic gonadotropin
testicular trauma. Genital examination
shows a 2cm fixed firm nodule on the d. Protein–specific antigen
lateral aspect of the right testicle. The e. The expression of tumor markers in
patient also has mild bilateral this lesion is variable
gynecomastia. An ultrasound confirms a
solid testicular lesion, and a CT scan
shows no apparent metastatic disease.
The testicle is removed, and the tumor is
revealed to be a choriocarcinoma.
A 15 year old boy presents to his family What tumor marker is elevated in all
physician after noticing a small, hard patients with this lesion?
nodule on testicular self-examination.
The patient denies pain in his testicles or a. Carcinoembryonic antigen
scrotum, or any difficulty or pain b. a-fetoprotein
associated with urination. He denies any
c. B-human chorionic gonadotropin
testicular trauma. Genital examination
shows a 2cm fixed firm nodule on the d. Protein–specific antigen
lateral aspect of the right testicle. The e. The expression of tumor markers in
patient also has mild bilateral this lesion is variable
gynecomastia. An ultrasound confirms a
solid testicular lesion, and a CT scan
shows no apparent metastatic disease.
The testicle is removed, and the tumor is
revealed to be a choriocarcinoma.
 Pathogenesis Arise in ovaries, testes, lower back, abdomen, chest and brain

Germ Manifestations •
•
•
Solid testicular mass, with or without pain
Solid ovarian mass incidentally discovered on abdominal UTZ
Visible mass in lower back, near the anus on an infant

Cell •
•
Respiratory distress associated with a mass inside the chest
Development of pubic hair, breast enlargement or vaginal bleeding
at a very young age

Tumor Subtypes BENIGN TERATOMA: requires no chemo

MALIGNANT TERATOMA: may require chemo, depend on stage
YOLK SAC TUMOR: high AFP, test for recurrence
CHORIOCARCINOMA: high bHCG, test for recurrence
EMBRYONAL CARCINOMA: among testes of adolescent boys
GERMINOMA: also seminoma in boys and dysgerminoma in girls
Diagnosis CT scan with contrast of chest, abdo and pelvis
Ultrasound of testes (testicular CA) and abdomen (ovarian CA)
AFP and bHCG
CBC, liver and kidney functions
Management Surgery
Chemotherapy
Radiation
Germ
STAGING THERAPY
TESTES OVARY NONTESTES
NONOVARY

Cell STAGE I Tumor

completely
resected
No therapy, unless it recurs Cisplatin,
Etoposide
Bleomycin

Tumor STAGE II Tumor resected,

small number of
Cisplatin,
Etoposide
Cisplatin,
Etoposide
Q3wks x 3
cycles
cells left behind Bleomycin Bleomycin
STAGE III Tumor has Q3wks x 3 Q3wks x 3 Cisplatin,
spread to lymph cycles cycles Etoposide
nodes Bleomycin
STAGE IV Tumor spread to Cisplatin, Q3wks x 4
the lung, liver or Etoposide cycles
others Bleomycin
Q3wks x 4
cycles
An 18 month old female presents for a well Which of the following is the most likely
baby consult. On ophthalmologic diagnosis?
examination, there is an asymmetric red
a. Rhabdomyosarcoma
reflex , with the left appearing normal and
the right appearing cream colored. b. Retinoblastoma
c. Neuroblastoma
d. Leukemia
e. Lymphoma
An 18 month old female presents for a well Which of the following is the most likely
baby consult. On ophthalmologic diagnosis?
examination, there is an asymmetric red
a. Rhabdomyosarcoma
reflex , with the left appearing normal and
the right appearing cream colored. b. Retinoblastoma
c. Neuroblastoma
d. Leukemia
e. Lymphoma
 Pathogenesis Most common primary intraocular malignancy in
Retino- Manifestations
kids
Leukocoria

blastoma Diagnosis
Scleral depression, pupillary dilation
Strabismus, red eye, glaucoma, pseudohypopyon
Indirect ophthalmoscopy
Genetic testing
Management Enucleation
Chemoreduction
Laser photocoagulation, cryotherapy, plaque
radiotherapy, thermotherapy
A 5 year old boy presents with fever, Which element of his disease is most likely to
pallor and bone pain, and is be accountable for his condition?
diagnosed with Acute Lymphoid
Leukemia following extensive a. Cardiac damage due to doxorubicin
laboratory work-up and bone marrow
biopsy. His lab tests reveal WBC of b. Incorrect dosing of anesthetic given during
bone marrow biopsy
240, Hemoglobin of 8.1 and platelet
of 79. Chemotherapy is initiated stat. c. Leukemic infiltrate of the kidney leading to
12 hours after, he develops acute decreased renal function
ventricular arrhythmia. He was d. Overhydration leading to acute renal
anuric for 8hrs despite IV fluids. failure
Electrolytes were Na 2.5 and K 8.9. e. Rapid destruction of leukocytes by
Urinalysis showed uric acid crystals. chemotherapeutic agents
A 5 year old boy presents with fever, Which element of his disease is most likely to
pallor and bone pain, and is be accountable for his condition?
diagnosed with Acute Lymphoid
Leukemia following extensive a. Cardiac damage due to doxorubicin
laboratory work-up and bone marrow
biopsy. His lab tests reveal WBC of b. Incorrect dosing of anesthetic given during
bone marrow biopsy
240, Hemoglobin of 8.1 and platelet
of 79. Chemotherapy is initiated stat. c. Leukemic infiltrate of the kidney leading to
12 hours after, he develops acute decreased renal function
ventricular arrhythmia. He was d. Overhydration leading to acute renal
anuric for 8hrs despite IV fluids. failure
Electrolytes were Na 2.5 and K 8.9. e. Rapid destruction of leukocytes by
Urinalysis showed uric acid crystals. chemotherapeutic agents
 Pathogenesis Metabolic complication after treatment of
neoplasm
Manifestations Hyperphosphatemia
Hypocalcemia
Hyperuricemia
Hyperkalemia

Tumor Lysis Diagnosis Laboratory TLS: At least 2 metabolic

abnormalities

Syndrome Clinical TLS: laboratory TLS with increased

creatinine, seizures, cardiac dysrhythmia,
death

Management Hydration
Allopurinol
Hemodialysis (severe cases)