Neoplastic disorders

Dr Omar Bawazir MRCP, MHPE

Characteristics of Childhood
neoplasms
Genetic factors play important role in
etilogy
Most forms arise from germinal tissues, as
opposed to the epithelial origin of most
cancer in adults
High sensitivity to chemotherapy and
radiation and thus a high expectation for
cure
Early metastatic spread, which makes local
therapy alone rarely successful

Cell life
Apoptosis

Proliferation

Neoplastic disorder

Fishbone
format

Complication
& Prognosis

Treatme
nt

Define

Mass
Fever

Proble
m

Preventi
on

Clinical
Picture

Etiolog
y

investigati
on

Pain
(headach,
and local
pain
Paraneoplas
tic
Pallor

TABLE 53.1 DISTRIBUTION (%) OF PEDIATRIC

CANCERS
Leukemia

30

CNS tumor

22

Lymphoma

10

Neuroblastoma

Soft tissue sarcoma

Wilms tumor

Osteosarcoma/Ewing sarcoma of 5
the bone
Germ cell tumor

Retinoblastoma

Hepatoblastoma

Leukemia: 1- define
Definition:
Cancer of white blood cells
is a clonal disease (originating in a single cell)
and arrest at a specific stage of normal
myeloid or lymphoid hematopoiesis

Accounts for 25 30% of all

childhood cancers

Types:
Acute:
Bone marrow blast > 20 -30% of bone
marrow NC
97% of all childhood leukemia
Lymphoblastic 75%
Myeloblastic 15 - 20%

Chronic:
Rare in children

3 % of childhood
It consist of:

CML: Philadelphia chromosome: positive Ph1 myeloid

leukemia
Juvenile myelomonocytic leukemia (JMML)

ALL

AML

3- Clinical Features
General Systemic effects:
Fever
Lassitude
Night sweating
Musculoskeletal symptoms in up to 2/3 of
cases
Arthritis may be the only presenting
symptoms
Bone pain particularly affecting the long
bones,
8% of patients had been misdiagnosed
with rheumatic fever or juvenile idiopathic
arthritis

Bone marrow involvement

effect

RBC: anemia:
Fatigability
Dyspnoea
Tachycardia
Pallor

Neutrophils:
Fever
Mouth ulcer
Infection

Platelets (thrombocytopenia):
Purpura
Easily bruising
Mucosal bleeding
In rare occasion internal bleeding

Extramedullary involvement

Lymphadenopathy
Splenomegaly
Hepatomegaly
CNS
Genitourinary Tract: periapism rare
Testis: occurs in 10% - 23% of boys
Ovary
kidneys: Hematuria, hypertension
Gastrointestinal:
Bone:
Skin: common with AML
Cardiac: infiltrate and haemorrhage found at autopsy
Lung: infiltrate, Haemorrhage

4-Investigations
1. CBC

2. Blood film: Blast cells

3. Hepato-Renal profile and uric acid
4. CXR
5. BM aspirate: Blast > 20% of nucleated
cells
6. Karyotype

Acute Lymphoblastic Leukemia types (FAB

classification)
L1

L2

Normal blood film

L3

Immunophenotype
Cluster of Differentiation (CD)

Immunophenotype
Cluster of Differentiation

Immunophenotyping of ALL and

Characteristic features
Pre-B cell accounts for 80% with cALL ag
(CD10)
Mature B-cell 1 2% have surface
immunoglobulin positive
T-cell accounts for 15 20% and
associated with:

Poor prognosis
Old age at presentation
High initial WBC count
Presence of extramedullary disease

Bone marrow Aspirate

Acute leukemia blasts > 20% of the bone marrow

nucleated cells

Special stain
(cytochemistry)
Sudan
Black

Acute myeloid
Leukemia

Periodic acid
Schif (PAS)

Acute
Lymphoblastic
leukemia

FAB Classification
ALL vs AML

Morphology
Ctyochemical stain
Immunophenotypes (CD markers)
Cytogenetic (Karyotype)
Subtypes of ALL/ AML
ALL: L1 (84%), L2 (15%), L3 (1%)
AML: AML0, AML1, AML 2, AML3, AML4,
AML5, AML6, AML7

Poor Prognostic factors of

ALL
Count > 50,000
lymphoma leukemia
Abnormal cytogenetic studies
t(9,22),
t(4,11)
Hypodiploid ALL < 45 chromosomes
CNS or testicular involvement
Induction failure

Acute Myeloid Leukemia

AML accounts for 1520% of acute
leukemia
Inherited conditions predispose to AML:

Downs syndrome
Fanconi anemia
Diamond Blackfan anemia
Kotsmann and Bloom syndromes

Exposure to drugs associated with an

increased risk of developing AML such as
Alkylating agents, epipodophyllotoxins, and
nitrosoureas
Ionizing radiation

Poor prognosis in AML

WBC > 100,000

Monosomy 7
Secondary AML
Minimal residual disease after
induction

5- Treatment of Acute
Leukemia
1- Supportive:

Infection, Anemia, Platelets transfusion

2- Specific:

Chemotherapy:
Radiotherapy
Bone marrow transplantation
Genetic therapy
Monoclonal antibody like anti-CD 20

3- Treatment of complications:

Febrile neutropenia
Tumor lysis Syndrome
Hyperviscosity

Neoplastic disorder

Fishbone
format

Complication
& Prognosis

Treatme
nt

Define

Mass
Fever

Proble
m

Preventi
on

Clinical
Picture

Etiolog
y

investigati
on

Pain
(headach,
and local
pain
Paraneoplas
tic
Pallor

CNS malignancy
The second most common malignancy of childhood, accounts
20% of all
Most arise from glial cells and tend not to metastasize outside the
CNS
Association with some conditions such as:
Neurofibromatosis type 1 (NF-1)
Tuberous sclerosis

ICP precedes locazied symptoms (ventricles and deep midline

structrues)
Common infratentorial (posterior fossa) tumors include the
following:
Cerebellar astrocytoma (usually pilocytic [low grade] but occasionally
invasive or high grade)
Medulloblastoma, the most common malignant brain tumor in children
Ependymoma
Brainstem gliomas (often diagnosed neuroradiographically without
biopsy; may be high or low grade)

General Signs and Symptoms of

Intracranial Tumors
Recurrent morning headaches that are
usually associated with vomiting,
coordination problems, ataxia, head tilt, and
visual problems.
Hemiparesis.
Mental disturbances somnolence,
irritability, personality or behavioral change,
or change in school performance.
Seizures usually focal.
Endocrine abnormalities

Major Signs and Symptoms of Spinal

Tumors
Back pain increased in supine position or with Valsalva
maneuver)
Resistance to trunk flexion
Paraspinal muscle spasm
Spinal deformity (especially progressive scoliosis)
Upper or lower UMNL
Bladder and bowel impairment
Sympathetic change (sweating)
Sensory impairment below level of tumor (30% of cases)
Extensor plantar responses (Babinski signs)
Sphincter impairment (urinary or anal)

Prognostic Features

Tumor location and

Extent of spread (stage)
Histology:
Immunohistochemical
Cytogenetic and molecular genetic
findings, and measures of mitotic
activity

Treatment
Surgery
Chemotherapy
Radiotherapy

EBV
TB
Leukemia
Lymphoma
Others
Clinical Picture

Etiology

Define

Neck
swelling

Prevention
Complication &
Prognosis

Treatment

Investigation

Lymphoma: Hodgkin disease

Common in immunodeficiency conditions

Association with EpsteinBarr virus (EBV).
Persistent large cervical Lymphadenopathy
Systemic symptoms: fever >38C , night
sweats, and unexplained weight loss > 10%
Pruritis
Eosinophilia
Very high cure rate
Staging: I IV and either A .or B symptoms
Histopathological prognostic factor depends
on predominance and depletion of
lymphocytes
alcohol-induced pain is unknown, but edema of lesions,
vasodilation and

5-Treatment
Chemotherapy:
Vincristin: neuropathy: paralytic ileus, drop foot
Doxorubicin: cardiac toxicity
Cyclophosphamide: myelosuppression,
haemorrhagic cystitis
Prednisolone

Radiotherapy (rarel used in children

because of):
Hypothyroidism
Radiation pneumonitis
spinal area, growth is stunted. Mental effect

Non-Hodgkin's Lymphoma
characteristics
is the third most common childhood malignancy
NHLs either B-cell or T-cell origin
The main histologic types are:
Lymphoblastic
Burkitt
large cell lymphoma

They are considered high grade

High incidence with congenital or acquired
immunodeficiency
Renal involvement mainly in lymphoblastic and Burkitt
lymphomas.
Tumor lysis syndrome.
Serum LDH is an important marker.

Lymphoblastic Lymphoma
Morphologically similar to the
lymphoblast of acute Lymphoblastic
leukemia
Massive Lymphadenopathy
Hepatosplenomegaly
Fewer than 20% lymphoblasts exist
in the marrow and the
malignant cells are found in the
lymph node biopsy

Burkitt Lymphoma

Endemic or sporadic.
Endemic:
1. in Africa
2. Affect jaw, orbit and others.
3. EB virus > 97%.
4. Blast are typically vacuolated

TABLE 53.1 DISTRIBUTION (%) OF PEDIATRIC

CANCERS
Leukemia
CNS tumor
Lymphoma
Neuroblastoma
Soft tissue sarcoma
Wilms tumor
Osteosarcoma/Ewing sarcoma of the
bone
Germ cell tumor
Retinoblastoma
Hepatoblastoma

30
22
10
8
7
6
5
3
3
1

1. Constipation
2. Organomealy
3. Flatus: Intestinal
obstruction

Abd
distension:

4. Fluid: Ascitis
5. Tumor:
Neuroblastoma,
Wilms,
Hepatoblastoma
6.
Define

Others

Proble
m

Preventi
on

Clinical
Picture

DD
Etiolog
y

Complication
& Prognosis

Treatme
nt

investigati
on

Neoplastic

Lymphoma
Neuroblastoma
Sarcomas (retroperitoneal, embryonal)
Wilms tumor (nephroblastoma)
Hepatoblastoma
Rhabdomyosarcoma
Ovarian tumor
Metastatic disease

Clinical Picture
Age
Neonates most of them are benign (common renal, teratoma)
Older children 50% are malignant

B-symptoms: fever >38, night sweating, weight loss >

10%
GIT and Genito-renal symptoms
Hypertension
Haematuria
Watery diarrhea

Metastasis (CNS, Bone marrow, lung, lymph node, and

liver)
Associations:
Clinical pictures: hemihypertrophy, aniridia, opsoclonus
Diseases

Neuroblastoma
Origin neural crest (adrenal
medulla)
Age: stage 4-S
Site:
Horner syndrome
Raccoon Eyes (Periorbital
ecchymoses)

Hypertension
intractable diarrhea
catechole amin (VMA &
HVA)
Opsoclonus myoclonus
Tumor cell DNA content, Nmyc protooncogene
Infant with stage 4-S Neuroblastoma with multiple
amplification
skin nodules, sometimes called the blueberry

Horner syndrome

Periorbital
ecchymoses

Wilms tumor
Asymptomatic mass rarely cross the
midline
5 10% bilateral
Haematuria
Hypertension (renin, rare vascular)
Certain congenital anomalies (is
associated with certain congenital
anomalies:

genitourinary malformations,
hemihypertrophy,
sporadic aniridia,
cryptorchidism,
Beckwith-Wiedemann syndrome,
Denys-Drash syndrome, and the
There is also a familial form of Wilms
tumor.
Polycythemia
Acquired VWD

CT-intra-renal mass

Hemihypertrophy
1. Wilms tumor
2. Adrenocortical
tumors
3. hepatoblastoma
4. Hamartmomas
5. Neurofibromatosis
6. Silver syndrome

13
yrs
mal
e

Define

Treatme
nt

investigati
on

Proble
m

Preventi
on

Clinical
Picture

DD
Etiolog
y

Complication
& Prognosis

Rhabdomyosarcoma
a soft-tissue malignant tumor of skeletal
muscle origin
painless, enlarging mass or s
symptoms related to obstruction of organs.
The most common sites of involvement
include:
Head, neck, or orbit (35%)
Extremities (24%)
GU tract (18%)
Trunk (11%)

Osteosarcoma
6% of all childhood malignancy
Age: around 15 years coincident with growth
spurt
Most common site is in the region of the knee
metaphysical. portion of the long bone
Pain
Swelling of the extremity and
pathological fracture
Tumor cells produce osteoid
Associated with retinoblastoma Oncogene (Rb)
and recessive Oncogene p53
Higher incidence in person treated with alkylating
agent and other bony disease

 Soft tissue extension 75%

sunburst appearance in 60%
Lytic lesion 30%
Mixed lesion 25%

What is the finding? Give 3 possible

causes?

Retinoblastoma
Presenting Signs and Symptoms
1. Leukocoria. termed white reflex = Unusual
appearance of the eye
2. Strabismus.
3. Decreased visual acuity.
4. Inflammatory changes.
5. Hyphema.
6. Vitreous hemorrhage, resulting in a black
pupil.
7. pain if associated with glaucoma

Liver cancer
hepatoblastoma and hepatocellular carcinoma.
Hepatoblastoma occurs in children aged 3 years or
younger.
Hepatoblastoma is associated with BeckwithWiedemann syndrome and familial adenomatous
polyposis.
Hepatocellular carcinoma occurs primarily in the 12to 15-year age-group but can be seen in children from
birth to 4 years of age. It is associated with hepatitis
B and hepatitis C, especially in children with
perinatally acquired infection
Increased fetoprotien

Chemotherapy complication

Steroid
Alkylating agents: decreased fertility and secondary tumor
Anthracyclines: cardiomyopathy, vesicant to skin
Asparaginase: pancreatitis, coagulation abnormalities, and
allergic reaction
Bleomycin: pulmonary fibrosis
Cisplatin: ototoxicity and renal toxicity
Cyclophosphamide: bladder irritation, syndrome of
inappropriate antidiuretic hormone secretion (SIADH)
Etoposide: secondary leukemia
Ifosfamide: Fanconi renal tubular acidosis, bladder irritation
Vincristine/vinblastine: neurotoxicity, vesicant to skin,
constipation

Treatment of neoplastic
Complications
Tumor lysis syndrome
Febrile neutropenia:

Empiric antibiotic: broad spectrum: to cover

both gram negative and positive bacteria
Anti-fungal
Anti-viral

Varicell-Zoster exposure:
Immunoglobulin
Acyclovir

Pneumocystis carinii: can be prevented

with trimethoprim-sulfamethoxazole
prophylaxis

The tail: Vaccination

Dont give live vaccines while the
child is immunocompromised: like
BCG, Viral vaccines
DD
Re-vaccinate children
after
Define
Clinical
Etiolog
completion
of treatment
Picture

Complication
& Prognosis

Treatme
nt

proble
m

Preventi
on

investigati
on

What are the findings and possible

diagnosis?
A