HEMATOLOGY IV DIFFERENCES BETWEEN PEDIATRIC AND CHILDHOOD

Dr. Maria Lita Fe P. Paclibar CANCERS

Parameter Children Adults
CANCER IN CHILDREN
• 2nd leading cause of death among 1-14 year olds Site Tissues Organs
in the US (10.6% of all deaths).
• Prevalence of Cancer Survivors age 19 years old Status at diagnosis 80% disseminated Local or Regional
or younger (90000-174000)
Early detection Usually accidently Improves with
education and
ANNUAL INCIDENCE OF MALIGNANT TUMORS screening
• 12.45/100,000 children under 15 years old
• Philippines: crude rate for childhood cancer is Screening Difficult Adequate
103 annual new cases per million children Response Most respond to Lower response to
(Equivalent to 3,500 new cases of childhood chemotherapy chemotherapy
cancer or almost 10 new cases each day)
Prevention Unlikely 80% preventable
INCIDENCE OF CANCER IN CHILDREN UNDER AND OVER
15 YEARS OF AGE, BY GROUPS AND SUBGROUPS IN RISK FACTORS FOR CHILDHOOD CANCER
THE INTERNATIONAL CLASSIFICATION OF DISEASES ➢ Ionizing radiation
TYPE OF CANCER <15 years >15 years -Exposure to X-rays during pregnancy
➢ Chemical and Drugs
ALL 23.5% 5.6%
a. Diethylstilbestrol- vaginal CA
AML 4.7% 4.3% b. Pesticide exposure- leukemia, NHL,
neuroblastoma
Hodgkin’s disease 3.6% 16.8% c. Benzenes- leukemia
d. Nitrous compounds in processed food and
NHL 5.7% 8.3%
tobacco- CNS tumors
CNS tumors 22.1% 9.8% e. Alcohol and diuretics- NBS, Wilm’s tumor
➢ Biologic factors
Neuroblastoma 0.9% 0.2% a. EBV- lymphoma
Retinoblastoma 3.2% 0%
b. HIV
c. Hep B and C
Wilm’s tumor 6% 0.3% d. HPV
➢ Genetic and familial factors- <5%
Hepatoblastoma 1.3% 0%
a. Down Syndrome- 10-30x acute leukemia
b. Klinefelter syndrome- 20x breast cancer,
Pediatric Cancer 30-50x GCT
• Acute Lymphocytic Leukemia (ALL) c. Li Fraumeni (p53) syndrome
• Brain Cancers ➢ Age
• Lymphomas
• Sarcomas of Soft Tissue & Bone HOW DOES CANCER DEVELOP?
Step 1: A mistake in the cell happens- Sooner or later,
Common Tumors by Age: 1st Year exposure to ultraviolet light, chemicals from the
• Most likely Congenital environment or even the byproducts of normal
• Embryonal Tumors metabolism damages one of the genes in a cell. In most
o Neuroblastoma cases, this does not lead to cancer.
o Wilm’s Tumor
o Retinoblastoma Step 2: The mistakes add up
o Rhabdomyosarcoma a. DNA Repair Genes- these genes make proteins
o Medulloblastoma that correct the errors that sometimes occur
whenever a cell copies its DNA. If repair can’t
Common Tumors by Age: 2-5 Years do their job, genetic mistakes start to
• Embryonal Tumors accumulate.
• Acute Leukemia b. Tumor Suppressor Genes- These restrain cell
• Non-Hodgkin’s Lymphoma growth and division. Their absence or
• Glioma inactivation takes the brakes off cell
multiplication.
Common Tumors by Age: Puberty c. Growth Genes- If the genes that regulate
• Bone Malignancy normal cell growth and division become stuck
• Hodgkin’s Disease to the “on” position, growth ensues
• Gonadal Germ Cell Tumors
• Carcinomas
Step 3: The cell turns cancerous- Free from normal - Brain tumors interfere with CSF circulation,
restraints, the now malignant cells break all the rules. and caused increased ICP
They divide uncontrollably, become less attached to
their neighbors and invade the space occupied by - Supratentorial tumors- vomiting 46%, HA 43%
normal cells.
- Infratentorial tumors- coordination difficulties
Step 4: The tumor’s appetite grows- In a process called 59%, vomiting 76%, HA 56%
angiogenesis, malignant cells secrete chemicals that
attract and promote formation of new blood vessels. -95% of children with HA and brain tumor had
With a steady supply of nutrients, the tumor can grow abnormal neurologic problems
without limits.

Step 5: The cancer spreads- Pieces if the tumor break Signs & Symptoms of a Child with Cancer
off and in a process called metastasis, migrate through • Childhood Cancer is difficult to diagnose in its
the blood and lymphatic systems. Eventually the early stages because most S/Sx are non-specific
runaway cells colonize other parts of the body and give & may mimic a variety of other more common
rise to distant tumors. childhood disorders.
• Some of the S/Sx associated with more
“Pediatric Cancer is not preventable, but it can be common Adult-Inset Malignancies are rare in
detected in early stages” children.
Developed countries- 80-90% survival rate • Obtaining the History is the 1st step in the
Philippines- <20% overall survival rate diagnostic process, with the Chief Complaint
being the most important initial clue.
Genes Involved in Oncogenesis • Family Medical History is of paramount
• Oncogenes – genes that when translated can importance when the diagnosis of malignancy is
result in malignant transformation of a cell. a possibility.
• Tumor Suppressor Genes – inactivation result o Parents, Siblings, 1st Cousins
to expression of a malignant phenotype. o List serious illnesses, Family Members,
• Proto-Oncogenes – cellular genes that regulate Ages, Congenital Anomalies, Cause of
cell growth, division, & differentiation & when Death for Deceased Members
altered become Oncogenes. o Malignancies
o 3 main mechanisms by which Proto- • Environmental Factors – exposure to Ionizing
Oncogenes transform into Oncogenes: Radiation & Oncogenic Viruses (e.g. HIV, EBV)
▪ Amplification
▪ Point Mutation Signs & Symptoms of Childhood Cancer Mimicking
▪ Translocation Normal Childhood Illness
• Generalized Malaise, Fever, Adenopathy
HOW TO ASSESS THE POSSIBILITY OF CANCER • Headache, Nausea, Vomiting
ASK • Febrile Seizure
✓ Has the child had fever for more than 7 days • Rhinitis, Epistaxis, Pharyngitis
and/ or heavy sweating? • Adenopathy
-Fever in a child with cancer is usually
associated with other symptoms such as bone Possible Malignancy
pain, weight loss and pallor • Lymphoma, Leukemia, Ewing’s Sarcoma,
Neuroblastoma
- Anemia + Purpura + Fever appears on 2/3 of • Brain Tumor (Leukemia)
leukemias • Soft Tissue Sarcoma

- If associated with hepatomegaly, Differential Diagnosis: Headache

splenomegaly, lymphadenopathy, • Brain Tumors interfere with CSF circulation &
hyperleukocytosis- leukemia is highly probable increased Intracranial Pressure.
• Supratentorial Tumors – Vomiting 46%,
-Lymphoma- most frequently causes prolonged Headache 43%
fever without significant findings on PE; may be • Infratentorial Tumors – coordination
associated with heavy sweating difficulties 59%, Vomiting 76%, Headache 56%
• 95% of children with Headache & Brain Tumor
✓ Have there been changes in the child, such as had abnormal Neurologic Findings.
loss of appetite, weight loss or fatigue in the
last 3 months? Conditions Suggesting the Need for Computed
-B symptoms of lymphoma- fever, night sweats, Tomography in Children with Headache
weight loss • Presence/Onset of Neurologic Abnormality
• Ocular Findings – Papilledema, Decreased Visual
✓ Has the child had headache recently? Acuity, Loss of Vision
 • Vomiting that is persistent, increasing in o LAD that predominates in Non-Cervical
frequency, or preceded by recurrent Headaches Areas is more suggestive of Malignancy
• Increased severity or frequency of Headache than the Head & Neck
• Recurrent monitoring of Headache or Headache o Left Supraclavicular – Abdominal
that repeatedly awaken a child from sleep o Right Supraclavicular - Pulmonary
• Short stature or deceleration of Linear Growth • Regional VS Generalized Enlargement –
• Diabetes Insipidus Generalized if enlarged in ≥ 2 contiguous Lymph
• Age ≤ 3 years old Node Areas
• Neurofibromatosis • Character – Cancerous masses are firm,
• Cured of Acute Lymphocytic Leukemia (ALL) rubbery, matted, no tenderness, erythematous,
with Irradiation of CNS as a part of initial warm, or fluctuating.
treatment • Need for Lymph Node Biopsy:
o Nodes that remain enlarged after 2-3
Primary Sites of Brain Tumors weeks of Antibiotics
• Infratentorial 43.2% o Nodes that have not diminished in size
• Supratentorial 40.9% after 5-6 weeks or do not return to
• Spinal Cord 4.9% normal size by 10-12 weeks
• Multiple Sites 11.0% o Enlarged Nodes associated with any
abnormal Chest Film finding.
Tumor Sites by Age • A child’s age offers important diagnostic
• 1st Year Supratentorial information & direction in evaluating enlarged
• 1-10 Years Infratentorial Nodes of the head & Neck Region for possible
• After 10 Years Supratentorial Cancer.
o < 6 years old – Neuroblastoma,
Brain Tumors Rhabdomyosarcoma, Non-Hodgkin’s
• Astrocytoma – most common Pediatric Brain Lymphoma Leukemia
Tumor o 7-13 years old – Non-Hodgkin’s
• Mixed Gliomas Lymphoma, Lymphosarcoma, Thyroid
• Ependymal Tumors Cancer, Rhabdomyosarcoma
• Choroid Plexus Tumors o > 13 years old – Hodgkin’s Disease
• Embryonal Tumors (PNET) – most common
Malignant CNS Tumor of childhood Differential Diagnosis: Thoracic Masses
• Pineal Parenchymal Tumors • Anterior Mediastinum – Lymphomas, Thymic
• Craniopharyngioma Masses, Teratomas, Angiomas, Lipomas, Thyroid
• Germ Cell Tumors Tumors
• Brainstem Tumors • Middle Mediastinum – Lymphomas, Metastatic/
• Metastatic Tumors - uncommon Infection-Related Lesions involving Lymph
Nodes, Direct Extension of Abdominal Malignant
Treatment Lesions, Pericardial Cysts, Bronchogenic Cysts,
• Surgery – purpose is three-fold Esophageal Lesions, Diaphragmatic hernias
o Provides Tissue Biopsy fro purposes of • Posterior Mediastinum – Neurogenic Tumors,
Histopathology Ewing’s Sarcoma, Lymphoma,
o Attains Maximal Tumor Removal Rhabdomyosarcoma
o Relieves increases ICP
o Stereotactic Biopsies allow Biopsy of Differential Diagnosis: Bone & Joint Pain
Deep-Seated Midline Tumors • Need for Radiograph if Bone/Joint Pain is
• Radiotherapy – Total Surgical Removal not persistent, abrupt in onset, occurs at night, &
possible in most Brain Tumors; in some Tumors, if associated with swelling, mass, or limitation
recurrence is high in spite of total removal of motion.
macroscopically • Radiographs are important in judging extent &
• Chemotherapy – Tumors with low Mitotic Index behavior of Skeletal Lesion but they should not
& small Growth Fraction are less sensitive to be used to make a definitive Diagnosis because
Chemotherapy there are NO PATHOGNOMONIC RADIOGRAPHIC
SIGNS OF MALIGNANT BONE LESIONS.
OBSERVE, FEEL AND IDENTIFY ASK
✓ Feel the neck, axilla and groin to look for ✓ Does the child have bone pain?
lymphadenopathy -Early symptoms of childhood cancer rarely
• Size – Lymph nodes are considered enlarged if > include pain except for malignancies involving
10 mm in its greatest diameter (Exception: bone or bone marrow
Epitrochlear Nodes > 5 mm, Inguinal Nodes > 15 -Pain precedes a soft tissue mass; persistent
mm) and intense bone or joint pain, abrupt in onset,
• Location – always abnormal in Posterior awakens a child at night, does not disappear
Auricular, Epitrochlear, & Supraclavicular over time
 -Pain from the bone tumors is unrelated to the OBSERVE, FEEL AND IDENTIFY
intensity of a possible injury ✓ Observe whether the child has severe palmar
-40% of leukemias have bone or joint pain as an or conjunctival pallor
initial symptom (erratic, intermittent, poorly - WHO children 6 months to 6 years are anemic
defined pain that can be confused with RHD) when their hemoglobin is lower than 11 g/dl
-any bone pain of disproportionate intensity to
the history of injury or without injury that lasts -Most frequent cause of anemia in children:
several days merits examination to rule out 1. Iron deficiency
neoplasm 2. Infections
3. Parasites
Osteosarcoma – most common Primary Malignant Bone 4. Malaria
Tumor in children & adolescents. 5. Oncologic diseases especially leukemia
• Highest incidence during Adolescent Growth
Spurt. -Compare the color of the child’s palm with
• Patients usually taller than their peers of your palm or with the palm of the other
similar age. children
• Patients with increased risk:
o Hereditary Retinoblastoma -Conjunctival pallor- if with conjunctivitis,
o Li-Fraumeni Syndrome pallor is replaced by conjunctival hyperemia;
o Rothmund-Thomson Syndrome examination of the conjunctiva can make
o Benign Conditions (Paget’s Disease, children cry
Enchondromatoses, etc.)
OBSERVE, FEEL AND IDENTIFY
Primary Sites of Origin ✓ Examine the child’s eyes to see if there are
• Femur 53% any abnormalities
• Tibia 26% -Leukocoria is considered synonymous with
• Humerus 12% retinoblastoma
• Fibula 5%
• Scapula 1% -Aniridia (photophobia and decreased vision)-
• Ileum 1% Wilm’s tumor
• Other 2%
-Acquired strabismus- brain tumor or
Treatment retinoblastoma
• Surgery + Chemotherapy – 65=75% 5-year
Disease-Free Survival -Heterochromia- NBS, iris melanoma
• Surgery – if used alone results to 90%
recurrence -Proptosis
o Biopsy ! Amputation/Limb Salvage
• Chemotherapy RETINOBLASTOMA
o Neodjuvant – Pre-Operative • Leukokoria – white Pupillary Reflex
o Adjuvant – Post-Operative • Strabismus – from poor vision secondary to
Macular Involvement
Poor Prognostic Factors • Red, Painful Eyes secondary to Intraocular
• Detectable Metastasis at Diagnosis Inflammation, Uveitis, or Vitreous Hemorrhage;
• Axial Skeletal Primaries (Skull, Vertebrae) Pain is unusual (usually secondary to Glaucoma
• Skip Lesions
• Children < 10 years old Diagnosis
• Elevated Alkaline Phosphatase & Lactic ❖ Does require a biopsy but is established by
Dehydrogenase characteristic ophthalmologic findings
❖ Orbital UTZ, CT or MRI- used to evaluate extent
OBSERVE, FEEL AND IDENTIFY of intraocular disease and extraocular spread
✓ Observe if the child has ecchymoses, ❖ Retinoblastoma + Pineal gland tumor= trilateral
petechiae or manifestations of bleeding retinoblastoma
-Uncommon sign of cancer in children ❖ Bone scan, CSF evaluation, BMA- only if
-usually related to thrombocytopenia secondary necessary
to marrow involvement, or impaired platelet Treatment
function due to drugs (NSAIDs for fever or pain) ❖ Primary goal- cure; secondary goal- preserve
-bruises or petechiae may not be related to vision
trauma and are too large for minor trauma ❖ Enucleation- if there is no potential useful
-coagulopathy common in acute promyelocytic vision
leukemia (M3), ALL, Lymphoma,NBS ❖ Laser photocoagulation or cryotherapy
❖ Chemotherapy
❖ External beam radiation
 • Histology: Fetal, Embryonal, or Mixed (Fetal
OBSERVE, FEEL AND IDENTIFY Histology carries a better prognosis)
✓ Look for acute and/or progressive focal • Alpha Fetoprotein (AFP) is elevated in almost
neurologic signs all Hepatoblastomas.
-Acute neurological problems- diagnosed recently
or during the visit Diagnosis
-Weakness • Plain Radiographs & Ultrasound of the Abdomen
-Asymmetries- cranial nerve dysfunction due to to characterize Heaptic Mass
mass effect • CT Scan/MRI to define extent of Intrahepatic
-Changes in consciousness, mental status or Tumor involvement.
behavior • CT Scan of the Chest & Bone Scan for
-Disorders of coordination balance and gait evaluation of Metastasis
-Difficulty speaking or visual field defects • Biopsy

OBSERVE, FEEL AND IDENTIFY Treatment

✓ Feel the abdomen and pelvis to look for • Cure depends on complete resection of Primary
masses Tumor
• All Abdominal Masses require workup. • Chemotherapy (Cisplatin, Vincristine, 5-
• In a high incidence of Renal cause for Fluorouracil, Doxorubicin)
Abdominal Mass, a thorough History that
focuses on the Urinary Tract is important. OBSERVE, FEEL AND IDENTIFY
• Newborn – Renal cause is important; if ✓ Look, feel and identify if there is any mass or
Malignant, most likely Wilms’ Tumor or enlargement in any region of the body
Neuroblastoma - Any enlargement of any organ or in any region
• Older Children – Leukemia/Lymphoma with of the body without inflammatory
Liver/Spleen involvement characteristics is suspicious for cancer
• Further studies depend on whether CBC is ➢ Malignant testicular neoplasms- <5
normal. years
• Rectal Examination is indicated if the child has ➢ Yolk sac tumors- <2 years
a normal absolute Neutrophil Count. ➢ Masses in the limbs- pain can precede
• Vaginal Pelvic Examinations in older the enlargement
adolescent girls; Bimanual Abdominal & Rectal ➢ Subcutaneous nodules- neuroblastoma,
Examinations in infants & younger girls acute leukemias, LCH
• Ultrasound of the Abdomen & Chest X-Ray
results may suggest the need for further tests Differential Diagnosis: Pancytopenia & Leukocytosis
such as CT Scan, IV Urography, Tumor Markers, • Pancytopenia – Anemia, Leukopenia,
Bone Marrow Aspiration, etc. Thrombocytopenia alone or in combination are
• HISTOLOGIC CONFIRMATIONIS ALWAYS common presenting signs of leukemia.
NECESSARY. o Any malignancy that involves the Bone
Marrow can produce Pancytopenia or
Germ Cell Tumors depression of only one of the Cell
• Most Malignant Tumors of the Gonads in Lines.
Children. o Other malignancies with Bone Marrow
• Sacrococcygeal Tumors occur predominantly in Involvement includes NBS, Lymphoma,
Female Infants. Ewing’s Sarcoma, & Rhabdomyosarcoma
• Testicular Germ Cell Tumors occur o Unless there is Marrow involvement,
predominantly before 4 years old & after Leukopenia is rarely a part of
Puberty. extramedullary malignancies.
• Undescended Testes increases the risk of
Testicular Cancer. • Leukocytosis – common in Acute Leukemias
• Germ Cell Tumors arise from Primordial Germ o Most Non-Malignant causes of
Cells; Non-Germ Cell Tumors arise from the Leukocytosis are caused by infections
Coelomic Epithelium (especially Staphylococcal &
• Germ Cell Tumors may contain Benign & Pneumococcal Infections)
Malignant Elements in different areas of the o Lymphoid Leukemoid Reactions
Tumor. (Infectious Lymphocytosis, Mumps,
Varicella, Adenovirus, Cytomegalovirus,
Hepatoblastoma & Pertussis)
• 50-60% of Hepatic Tumors in Children are o Eosinophilic Leukemoid Reactions
Malignant. (Parasitic Infections, Hypereosinophilic
• 65% of Malignancies are Hepatoblastomas. Syndrome, Polyarteritis Nodosa, Allergy,
• Usually Children < 3 years old Hypersensitivity Reaction)
 ▪ Malignant Cause – Hodgkin’s
Disease, Acute Lymphocytic
Leukemia, Acute Myeloid
Leukemia
o White Blood Cell Count > 100,000/mm3
almost always reflect a Leukemia.

Indications for Bone Marrow Examination

• Atypical/Blast Cells on Peripheral Blood Smear.
• Depression of > 1 Blood Cell Line without
obvious explanation.
• Association with unexplained
Lymphadenopathy/Hepatosplenomegaly or a
Thymic Mass.
• Absence of an infectious cause for Blood
Abnormality.

Differential Diagnosis: Bleeding

• Uncommon initial sign of Cancer in children.
• Usually related to Thrombocytopenia secondary
to Bone Marrow involvement or impaired
Platelet function due to Drugs (NSAIDs for
Fever/Pain)
• Coagulopathy common in Acute Promyelocytic
Leukemia (M3), Acute Lymphocytic Leukemia,
Lymphoma, & NBS
• Work-Up: Complete Blood Count, Activated
Protein C (APC), Bone Marrow Aspiration,
Prothrombin Time, Activated Partial
Thromboplastin Time, Fibrinogen Level, Fibrin
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