08/01/21

MUST KNOW TOPICS

— Anemias — Neuroblastoma
PEDIATRIC —
—
Iron deficiency
Aplastic
— Wilm’s tumor
— Lymphoma
HEMATOLOGY ONCOLOGY PEARLS —
—
Physiologic
microcytic.,macrocytic, — Teratoma
hypochromic — Brain tumors
— Leukemias — Hepatoblastoma
— ALL, AML, CML — Osteosarcoma
— Idiopathic
thrombocytopenic
purpura
— Hemophilia
— Thalassemias

ANEMIA ANEMIA

IRON-DEFICIENCY ANEMIA ANEMIA

NORMO HYPOCHROMIC HYPOCHROMIC
CHROMIC MICROCYTIC MACROCYTIC
NORMOCYTIC
Acute blood loss Iron deficiency Folic acid
deficiency
RBC sequestration Pyridoxine Vitamin B 12
deficiency deficiency
Aplastic anemia Thelassemia Liver disease

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ANEMIA
NORMOCHROMIC HYPOCHROMIC HYPOCHROMIC
NORMOCYTIC MICROCYTIC MACROCYTIC
ANEMIA
Hemolysis due to Lead poisoning Hypothyroidism
extrinsic RBC MEGALOBLASTIC MICROCYTIC
abnormalities FOLIC ACID DEF VITAMIN B 12 DEF (Iron Deficiency)

(infection/ HPN/ MEAN AGE 4-7months 4-5 months 9-24 months

HUS etc.)
Hemolysis due to Chronic disease Thiamine deficiency SIGNS/SYMPTOMS Irritability Failure to thrive Iiritability
Failure to thrive Smooth tongue FTT
intrinsic RBC Chronic diarrhea Neurologic Etc.
abnormality Common among: symptoms
(Hemoglobinopathi 1. pregnant Common among:
women 1. Vegetarians
es/enzyme 2. On anti-seizure 2. Pernicious
deficiency etc.) 3. On anemia
methotrexate + SCHILLING TEST
Copper deficiency Myelodysplasia
TREATMENT FOLIC ACID VITAMIN B12 IRON

PHYSIOLOGIC ANEMIA OF INFANCY APLASTIC ANEMIA

CONSTITUTIONAL ACQUIRED
PRETERM FULLTERM
ETIOLOGY Chromosomal anomalies 1. Drugs
2. Parvovirus
3. Hepa B/C
ONSET 3-6 weeks of age 8-12 weeks 4. CMV/HIV
PATHOLOGY Chromosome breaks Peripheral pancytopenia
USUAL HGB 7-9 g/dl 9-11 g/dl + aplastic bone marrow
CONCENTRATION
SIGNS &SYMPTOMS Depends on the anomaly Anemia
Leukopenia
Thrombocytopenia
RBC LIFESPAN 40-60 days 120 days
COMPLICATION Leukemia and other Infection/ bleeding
cancers
TREATMENT IRON AND FOLIC ACID AT SAME AT 4 MONTHS OLD
4-8 WEEKS TREATMENT Steroids/androgens Bone marrow transplant

IDIOPATHIC THROMBOCYTOPENIC IDIOPATHIC THROMBOCYTOPENIC

PURPURA PURPURA
• Most common cause of acute onset • CLINICAL MANIFESTATIONS:
thrombocytoenia in an otherwise normal child – Previously healthy 1-4 year old child
• 1-4 weeks post viral infection in 50-65% – Sudden onset generalized petechiae and purpura
• Autoantibody formation (autoimmune) – Gum and nose bleeding
– Markedly decreased platelet count
– Previous viral infection
– Normal PE other than peteciae and purpura
– Hepatosplenomegaly is rare

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IDIOPATHIC THROMBOCYTOPENIC IDIOPATHIC THROMBOCYTOPENIC

PURPURA PURPURA
• Laboratory findings: TREATMENT
– Severe thrombocytopenia (<20 x 10 9/L) • IV Immunoglobulin
– Normal wbc, diff count, hemoglobin values – Rapid rise in PC in 95% in 48 hours
– Bone marrow show normal erythropoiesis, • Prednisone
granulopoiesis and normal or increased
megakaryocytes • IV anti-D therapy
• Platelet transfusion
• Splenectomy

HEMOPHILIA HEMOPHILIA
• Most common severe inherited bleeding disorder Signs and symptoms:
• Hemophilia A(Factor VIII deficiency) • Easy bruising
• Hemophilia B (Factor IX deficiency) • Bleeding from minor trauma
• Factors VIII+IX+Ca+Phospholipid=Factor X • HEMARTHROSES = hallmark of hemophilia
– Ankle- most common site in toddlers
activation
– Knees and elbows in older child and adolescent
• Intracranial hemorrhage in neonates (occasional)
Tissue injury platelet plug fibrin • Bleeding at iliopsoas muscle may cause severe
formation concealed bleeding and result to hypovolemic
Slow and weak clot formation bleeding shock

HEMOPHILIA HEMOPHILIA
• Screening tests: Treatment:
– Normal CT, BT, Platelet, PT • Replacement therapy
– Factor VIII concentrate
– 2-3x prolonged than normal PTT – Factor IX concentrate
• Supportive care
• Confirmatory tests: • Prophylaxis
– Prevention of trauma
– Factor VIII and Factor IX assay
– Splinting
– Avoid NSAIDS
– Hepatitis B vaccination

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CANCER AND BENIGN TUMORS LEUKEMIA

• < 1% of all cancer occur in children <18y.o. • Most common cancer in chidren
• 2nd leading cause of death in children • 41% of all cancer
• Most common cancer 1. ALL 77%
1. ALL 2. AML 11%
2. Brain cancer 3. CML 2-3%
3. Lymphoma 4. JCML 1-2%
4. Bone & soft tissue sarcoma

LEUKEMIA ALL AML CML

ALL AML CML •Fever, fatigue, •BM failure •Greatly enlarged
•Most common •11% of leukemia •2-3% of bone pain •Subcutaneous spleen
•BM failure nodule or blueberry •Mild anemia
leukemia leukemia
•LAD, muffin •Thrombocytosis
•2- 6 years old hepatosplenomegal •Chloromas •Initial chronic
•More in males & y •Gingival phase of increased
kids with •CNS leukemia hyperplasia mature WBC ending
chromosomal •DIC with blast crisis
anomalies (hyperuricemia,neu
ro sx)
unknown cause Ionizing radiation
•Chemotherapy Chemotherapy •Chemotherapy
Radiation (+) Philadelphia
EBV chromosome

LYMPHOMA LYMPHOMA
HODGKIN’S NON-HODGKINS
•15-19 years old
•Black
•White
•Burkitts lymphoma
HODGKIN’S NON-HODGKINS
•Male
•EBV
•CXR/ CT scan •Biopsy
•(+) Reed Sternberg Cell –hallmark of HL; •T/B cells affected •Excision biopsy •LDH α tumor burden
large cell with multiple nuclei
•4 histologic types
•3 histologic types
1. Lymphobalstic
•CBC/ESR
1. Lymphocytic predominance
2. Nodular sclerosing
2. Small non-cleaved cell (Burkitt’s &
Non-Burkitts)
•BMA for staging
3. Mixed cellullarity 3. large cell lymphoma
4. Lymohocytic depletion

•Spreads to LN, liver, spleen, BM, brain
•1° symptom-painless, firm neck LAD
•Constitutional symptoms (fever etc)
•Impaired immunity
•Lymphoblastic- intrathoracic mass with
•Staging ( ANN ARBOR) •St. Jude staging
chest pain & dyspnea, SVC sybdrome with
bone, CNS, testicular spread
•SNCCL- abdominal mass with pain and
bowel changes
•LCL- abdominal mass

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HODGKIN’S NON-HODGKINS Neuroblastoma is a condition characterized by

the following:
•Chemotherapy •Surgery
•Radiation therapy •Multiagent
chemotherapy A. Malignancy most frequently diagnosed in
•60% survival rate NHL UNLIKE infancy
•90% cure HODGKIN’S IS TREATED B. Mixed embryonal neoplasm composed of
AS A MULTISYSTEMIC three elements: blastoma, epithelia and stroma
DISEASE C. Classically presents with leukocoria
D. Diagnosis does not require a biopsy but is
established characteristical clinical findings

NEUROBLASTOMA
• Epidemiology
– Embryonal CA of the PNS
– 3rd most common CA in young kids
– Most common cancer in infants
• Pathology
– Poorly differentiated neuroblastoma
– Similar to other ROUND CELL TUMORS (NHL/
Ewings/ Rhabdomyosarcoma)
NEUROBLASTOMA
• Signs & Symptoms
– Any site of the PNS
– Abdomen (retro or adrenal PNS) primarily
– Firm nodular mass in the flank with hge or
calcification (NOT SEEN IN WILMS’)
– Abdominal pain + Horner’s Syndrome (ptosis,
miosis, anhydrosis) + symphatetic symptoms
– Metastasize to bone, skull, BM, liver, LN, skin

Neuroblastoma NEUROBLASTOMA
Neuroblastoma can present as “blueberry muffin”
spots on the skin of neonates or as periorbital — Diagnosis
ecchymosis in older children. 1. VMA/HVA in urine
2. MRI
3. Biopsy
— Treatment
— Surgery and chemotherapy

• The signs and symptoms of neuroblastoma

reflect the tumor site and extent of disease

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A 5-year-old boy was brought to the OPD for WILMS TUMOR

frequent vomiting and abdominal distention.
He has had poor appetite for almost one month
and would complain of constipation and reddish
urine. On PE, BP= 130/90, T= 38.2C. You
palpated a mass on the right side of the
abdomen which was firm, not movable and non-
tender. What is your diagnosis?
a. Rhabdomyosarcoma
b. Hirschsprung’s disease
c. Impacted feces
d. Wilms’ tumor
• The most common initial clinical presentation
for WT is the incidental discovery of an
asymptomatic abdominal mass by parents
while bathing or clothing an affected child or by
a physician during a routine physical
examination
• Hypertension is present in approximately 25%
of tumors at presentation
• Abdominal pain, gross painless hematuria, and
fever are other frequent findings at diagnosis

NEPHROBLASTOMA NEPHROBLASTOMA
• Epidemiology • Signs & Symptoms
– 6% of cancer in kids – Primary sign: painless firm abdominal mass that
– 2-5 years old crosses midline
– 2nd most common abdominal cancer in kids – Abdominal pain, vomiting
• Pathology – Hematuria, hypertension
– Mostly sporadic with rare familial disease – Bone pain, bluish subcutaneous nodules
– Orbital proptosis and periorbital ecchymoses
– Metastasize to lungs (primary) and liver

NEPHROBLASTOMA WILMS TUMOR

• Associated abnormality (WAGR)
— Diagnosis
1. CXR
2. CT SCAN
3. Biopsy
— Treatment
— Surgery, Radiotherapy and chemotherapy

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12 year male with persistent right knee pain after

playing soccer, with limb pain causing him to OSTEOSARCOMA vs EWING SARCOMA
stop school; unresponsive to oral Paracetamol

A 15 year old consulted for arm swelling and pain. Xray

showed sclerotic destruction of the proximal humerus
with sunburst pattern. The most likely diagnosis is:

a. Osteosarcoma
b. Ewing’s sarcoma
c. Rhabdomyosarcoma
d. Enchondroma

SUNBURST PATTERN SUNBURST PATTERN

METAPHYSIS OF LONG BONES METAPHYSIS OF LONG BONES
OSTEOSARCOMA

ONION-SKINNING PATTERN ONION-SKINNING PATTERN

DIAPHYSIS OF LONG BONES DIAPHYSIS OF LONG BONES
SMALL ROUND CELL TUMOR SMALL ROUND CELL TUMOR
EWING SARCOMA

OSTEOSARCOMA OSTEOSARCOMA
• Epidemiology • Signs & Symptoms
– Peak during adolescence – Primary sign: LOCAL pain and swelling and usually
– More in males with history of trauma
– All races – Limitation of joint motion, effusion, warmth
• Pathology
– Spindle-cell producing osteoid
– Metaphyses of long bones
– Primarily on the distal femur

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OSTEOSARCOMA Tumor Age Clinical signs Labs

Wilms Preschool Unilateal Hematu
— Diagnosis tumor flank mass, ria;
1. CBC= normal aniridia, bone
2. Increased LDH and alkaline phosphatase hemihypertro scintigr
3. Xray- lytic lesion of the bone (SUNBURST phy aphy
PATTERN) Neuroblast Preschool GIT/GUT VMA
4. Biopsy oma obstruction,
— Treatment rocoon-eyes,
— Surgery, and chemotherapy myoclonus

Tumor Age Clinical signs Labs REVIEW QUESTIONS

Non- >1 year Intussusception Increased
hodgkin’s in >2yo child urate; Which of the following does not present as
biopsy hypochromic, microcytic anemia?
Germ cell/ Pre-school; Girls: hCG
teratoma teens abdominal pain,
vaginal a. Iron defieciency c. chronic renal failure
bleeding b. Thallassemia d. sideroblastic anemia
Boys: testicular
mass
Hepatoblastoma Birth-3year Large, firm liver AFP

Adoloscents who adhere to strict When does physiologic anemia of

vegetarian diet will have the following preterm infants occur?
disorder
a. 3-6 weeks of age c. 9-12weeks of age
a. Microcytic anemia c. normocytic anemia
b. 6-8 weeks of age d. 12-16 weeks of age
b. macrocytic anemia d. hemolytic disorder

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Children with factor VIII or IX Which of the following is incorrect

deficiency may present with referred regarding Idiopathic
pain in the groin that represent Thrombocytopenic purpura?
significant blood volume loss in which
muscle? a. hepatosplenomegaly c. sudden onset
generalized petechiae
a. Gluteus muscle c. iliopsoas muscle b. History of previous d. spontaneous
viral infection resolution in 6 mos
b. Obturator muscle d. gastrocnemius
muscle

When does physiologic anemia of Blood component indicated for

term infants occur? transfusion in acute idiopathic
thrombocytopenic purpura

a. 3-6 weeks of age c. 9-12weeks of age

a. Fresh frozen plasma c. cryoprecipitate
b. 6-8 weeks of age d. 12 weeks old
b. platelet concentrate d. Whole blood

Which of the following statements is Prolonged antibiotic therapy can result

true regarding Hemophilia A? to bleeding with the following
laboratory results:
a. Bleeding occurs mostly in the skin and
mucous membranes
b. Mode of inheritance is by autosomal a. Prolonged PT, normal PTT c. normal PT and
recessive transmission PTT
c. Vitamin K administration is the treatment of
choice b. Prolonged PT and PTT d. Normal PT,
d. Clotting factor VIII is deficient prolonged PTT

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Recurrent gum bleeding and

menorrhagia were noted in a 15 yo Pallor with pancytopenia is seen in:
female. CBC and platelet count were
normal. PT was normal but BT and PTT
were prolonged. The most likely a. Lymphoma c. aplastic anemia
diagnosis is:
a. ITP c. transient TP b. leukemia d. thalassemia

b. hypoprothrombinemia d. von Willebrand dse

It is the most common primary Which of the following statements

malignant bone tumor in children and about Wilms tumor is correct?
adolescents which shows a “sunburst”
pattern on x-ray: a. It is associated with hemihypertrophy and
aniridia
a. Ewing sarcoma c. osteochondroma b. It causes hypertension by releasing
catecholamines
b. osteosarcoma d. osteoblastoma c. It commonly presents with proteinuria
d. It is more common in older children and
adolescents

The mainstay of treatment for acute The most common malignancy in

lymphoblastic leukemia is: children and adolescents is

a. chemotherapy c. antibiotic therapy a. Brain tumor c. neuroblastoma

b. Blood transfusion d. bone marrow transplant b. Lymphoma d. leukemia

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Hypercellular bone marrow is Abdominal tumors in children with

associated with: increase HCG include:

a. Nutritional anemia c. acute leukemia

a. Neuroblastoma c. hepatoblastoma
b. Aplastic anemia d. anemia of chronic
disease b. Teratoma d. non-Hodgkin’s
lymphoma

Delayed sequela of therapy in

Grapelike mass of tumor tissue
childhood malignancy include:
bulding through the vaginal orifice is
a. Neuroblastoma c. fibrosarcoma
a. leukoencephalopathy c. metabolic d/o
b. Hodgkin’s lymphoma d. sarcoma botryoides
b. bone marrow suppression d. renal function
impairment

Which of the following has the best

over-all survival rate? _____ is an X-linked recessive syndrome
characterized by atopic dermatitis,
thrombocytopenic purpura with normal
a. Wilms tumor c. hepatoblastoma appearing megakaryocyte but small defective
platelet and undue susceptibility to infection
b. Non-Hodgkin’s d. neuroblastoma
lymphoma a. Ataxia-telangiectasia
b. Cartilage hair hypoplasia
c. Wiskott Aldrich syndrome
d. Autoimmune lymphoproliferative syndrome

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WISKOTT-ALDRICH SYNDROME WISKOTT-ALDRICH SYNDROME

• THROMBOCYTOPENIA AND ECZEMA
• X-linked recessive
• The abnormal gene, on the proximal arm of the X
chromosome at Xp11.22-11.23 Thrombocytopenia +
Eczema +
• Patients often have prolonged bleeding from the
circumcision site or bloody diarrhea in infancy. Infection +
• Atopic dermatitis and recurrent infections usually develop
during the 1st yr of life. WASP mutation
• The predominant immunoglobulin pattern is a low serum
level of IgM, elevated IgA and IgE, and a normal or slightly low
IgG concentration.
• should be given monthly infusions of intravenous immunoglobulin (IVIG)
regardless of their serum levels of the different immunoglobulin isotypes.

AUTOIMMUNE
_____ the genetic defect in most patient is a germ LYMPHOPROLIFERATIVE SYNDROME
• also known as Canale-Smith syndrome
line or somatic mutation in the Fas gene which
• disorder of abnormal lymphocyte apoptosis leading
produces a germ cell receptor of the tumor
to polyclonal populations of T cells
necrosis factor superfamily (TNFRSF6) which
when stimulated by its ligand will produce
• characterized by autoimmunity, chronic persistent or
programmed cell death.
recurrent lymphadenopathy, splenomegaly,
hepatomegaly (in 50%), and
a. Ataxia-telangiectasia hypergammaglobulinemia (IgG, IgA).
b. Cartilage hair hypoplasia
c. Hyper IgE syndrome
d. Autoimmune lymphoproliferative syndrome

Hyper-IgE Syndrome
Clinical features are staphylococcal abscess,
• recurrent severe staphylococcal abscesses of the
pneumatocoele, osteopenia, unusual facial
skin, lungs, and other sites and markedly elevated
features, with delay shedding of the primary levels of serum IgE
teeth and recurrent fractures and scoliosis
• The characteristic clinical features of the autosomal
a. Wiskott-Aldrich syndrome dominant form of the hyper-IgE syndrome are
b. Cartilage hair hypoplasia staphylococcal abscesses, pneumatoceles,
osteopenia, and unusual facial features.
c. Hyper IgE syndrome
d. Autoimmune lymphoproliferative syndrome

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___ is an autosomal recessive disorder Chediak Higashi Syndrome

characterized by increased susceptibility to
infection due to degranulation of neutrophil,
neuropathy, light-skin and silvery hair with solar
sensitivity and photophobia, oculocutaneous
albinism, mild bleeding diathesis
• increased susceptibility to infection caused by
defective degranulation of neutrophils, a mild
bleeding diathesis, partial oculocutaneous albinism,
progressive peripheral neuropathy, and a tendency
to develop a life-threatening form of
hemophagocytic lymphohistiocytosis

a. Chediak Higashi syndrome • have light skin and silvery hair and frequently
b. Leukocyte Adhesion Deficiency complain of solar sensitivity and photophobia
c. Autoimmune Lymphoproliferative Syndrome
• High-dose ascorbic acid (200 mg/day for infants,
d. Ataxia Telangiectasia 2,000 mg/day for adults) may improve the clinical
status of some children in the stable phase.

CONGENITAL THYMIC APLASIA

• DiGeorge Syndrome
• results from dysmorphogenesis of the 3rd and 4th
pharyngeal pouches during early embryogenesis,
leading to hypoplasia or aplasia of the thymus and
parathyroid glands.
• suggested by hypocalcemic seizures during
the neonatal period
• Microdeletions of specific DNA sequences
from chromosome 22q11.2

CATCH 22 Syndrome Severe Combined Immunodeficiency

DiGeorge Syndrome • absence of all adaptive immune function and, in
some, a lack of B cells and natural killer (NK) cells
Cardiac abnormalities
Abnormal facies, • All patients with SCID have very small thymuses (<1
Thymic hypoplasia, g) that usually fail to descend from the neck,
contain no thymocytes, and lack corticomedullary
Cleft palate, distinction
Hypocalcemia
Chromosome 22 • Affected infants present within the 1st few mo of
life with recurrent or persistent diarrhea,
pneumonia, otitis media, sepsis, and cutaneous
infections.

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Severe Combined Immunodeficiency

• Persistent infections with opportunistic
organisms including Candida albicans,
Pneumocystis jiroveci, parainfluenza 3 virus,
adenovirus, respiratory syncytial virus, rotavirus
vaccine virus, cytomegalovirus, Epstein-Barr
virus (EBV), varicella- zoster virus, measles virus,
MMR-V (measles, mumps, rubella, varicella)
vaccine virus, or bacillus Calmette-Guérin (BCG)
lead to death.

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