PEDIATRIC

MALIGNANCIES

Dr.Imad Dweikat
Pediatric Consultant
Makassed I.C Hospital
Acute Lymphoblastic Leukemia
The most common malignancy of childhood
77% of cases of childhood leukemias
Peak incidence in patients aged 2-6 years.
More common in certain genetic syndromes as
Down syndrome, ataxia-telengiectasia and
Fanconi syndrome
Interactions between genetic and environmental
factors.
Improvement in diagnosis and treatment have
produced cure rates that now exceeds 70%

Clinical Manifestations
Initially nonspecific:
Anorexia, fatigue, irritability, low-grade fever and
bone and joint pain

With progression: signs and symptoms of bone
marrow failure
Physical Findings:

Pallor
Infection
Bone&Jt dis
Other metas.
Rarely,increased
ICP
Lab Studies:
Basic Labs: Peripheral smear
CBC
PT, PTT,
Fibrinogen and
D-dimers (DIC)

Describe this blood film------->
( RBS IS 2/3 the size of the
lymphocyte)


Bone marrow:
ALL is diagnosed when >25%
of bone marrow cells are
homogenous population of
lymphoblasts
A complete morphologic,
immunologic and genetic
examination of the bone
marrow is necessary for
diagnosis of ALL
L1: Lymphoblasts are small
with scanty cytoplasm



L2:
Cells are larger and
pleomorphic with
increased cytoplasm,
irregular nuclear
shape and prominent
nucleoli
L3:
Cells have finely stippled
and homogenous nuclear
chromatin, prominent
nucleoli and deep blue
cytoplasm with prominent
vacuolization
Known as Burkitt leukemia
and is one of the most
rapidly growing cancer in
humans and requires a
different therapeutic
approach
Staging of ALL is partly based on CSF examination.
If lymphoblasts are found and the CSF leukocyte
count is elevated, overt CNS or meningeal
leukemia is present indicating a worse stage and
additional CNS & systemic therapy are indicated.
Morphology alone is usually adequate for
diagnosis, but the other studies are essential for
disease classification which may have a major
influence on the prognosis and the choice of
therapy.
Imaging studies:
Chest radiography: For mediastinal mass
Testicular ultrasound: If testes are enlarged
Renal ultrasound: To assess for ( Tumor lysis
syndrome )
Bone and Joint radiography
Treatment:
Combination Chemotherapy:
Consists of remission induction, CNS therapy, and
maintenance phase.
Different approaches based on estimated clinical
risk of relapse.
Prognosis:
Long term survival in most children(>80% after 5 years)
Poor prognostic factors:
1. Age < 1 year or > 10 years at diagnosis
2. Leukocyte count > 50,000-100,000 at diagnosis
3. Slow response to initial therapy
4. L3 morphology
5. Specific chromosomal abnormalities: t(9;22), t(4;11)
6. Mediastinal mass( most commonly seen in adolescents)
7. CNS leukemia
Age 1-10 y at diagnosis, leukocyte <50,000,Hyperdiploidy,
rapid response to therapy are favorable characteristics
Acute Myelogenous Leukemia
Suggestive Clinical Manifestations:



Blueberr
y
muffin
Exramedullary aggregates
Of blast cells. May occur in
Absence of apparent B.M
Involvement in M2
Of AML
DIC
Skin lesion of AML
Hodgkin Disease
One of the most common cancers in children.
The role of EBV is supported by serologic studies and
frequent presence of EBV genome in biopsy material.
Increased risk with pre-existing congenital or acquired
immunodeficiency. Cellular immune impairment is seen in
most newly diagnosed cases.
H.D arises in lymphoid tissues and spreads to adjacent
lymph node areas.
Hematogenous spread:Liver, spleen, bone, bone marrow
and brain
Cytokines may be responsible for the systemic symptoms.
Pathogenesis:
Reed-Sternberg cell:
Is the hallmark of
Hodgkin disease
although similar cells
are seen in infectious
mononucleosis, and
NHL.



Clinical Manifestations:
The most common:
Painless, firm cervical or
supraclavicular
lymphadenopathy
Anterior mediastinal mass
Axillary or inguinal lymph is
uncommon and HSM is rare
Airway obstruction, pleural or
pericardial effusion, hepatic
dysfunction or bone marrow
infiltration
Nephrotic syndrome is a rare
but recognized presentation


No signs of
Inflammation
Or
infection
Clinical Manifestations (cont):
Systemic symptoms: Unexplained fever
Night sweats
Weight loss
Pruritus, anorexia, lethargy

Concomitant tuberculous or fungal infections may
complicate Hodgkin disease

Diagnosis:
CXR: For mediastinal
mass
Excisional biopsy: FOR
Light microscopy
Immunocytochemical,
molecular and cytogenetic
studies Then
Staging:* CBC, ESR, Serum
copper & Ferritin
* Chest CT scan
* Abdominal CT/MRI
* Gallium 67 scan



staging

Neuroblastoma
An embryonal cancer of the peripheral
sympathetic nervous system
The third most common pediatric cancer.
The most frequently diagnosed neoplasm in
infants and 1/3 of neonatal malignancies
The median age at diagnosis is 2 years. 90%of
cases are diagnosed before 5 years of age.
It is one of small round cell tumors. Others are
rhabdomyosarcoma, Ewing sarcoma, and non-
Hodgkin lymphoma
Familial NB is found in 1-2% of cases

Clinical Manifestations
NB may arise at any site of
sympathetic nervous
system tissue.
Manifestations reflect the
site and extent of disease.
Most cases arise in the
abdomen either in the
adrenal gland or
retroperitoneal
sympathetic ganglia


NB may originate in the chest, superior cervical
ganglion causing Horner syndrome and paraspinal
region. Metastasis may produce proptosis and
periorbital ecchymoses.


Clinical Manifestations (cont):
The most common sites of metastasis are:
Long bones & skull, b.marrow, liver, lymph nodes and skin.
NB may present as paraneoplastic syndrome of autoimmune
origin: Opsomyoclonus ( dancing eyes and dancing feet ).
The primary tumor is in the chest or abdomen and no brain
tumor.
Some NB produce catecholamines ------- Sweating and
hypertension
Some release vasoactive intestinal peptides--------
Secretory diarrhea
Children < 1 year of age may present with subcutaneous
tumor nodules, massive liver involvement and a small
primary tumor without bone involvement (stage 4S).

Diagnosis:
Plain radiographs/MRI/CT scan (as mentioned)
Elevated tumor markers in 95% of cases:
( VMA AND HVA in urine )
NB can be diagnosed in a typical presentation
without a primary tumor biopsy if neuroblasts are
found in bone marrow and elevated urine VMA or
HVA.
Bone scan: For metastasis
WILMS TUMOR( nephroblastoma )
Is a complex mixed embryonal neoplasm of the kidney.
Usually occurs in children 2-5 years of age, but may occur at
any age including neonates.
The second most common malignant abdominal tumor in
children.
The incidence of bilateral Wilms tumor is 7%
1-2% are familial, inherited as autosomal dominant: Lower
age at DX and higher frequency of bilateral disease.
Congenital anomalies are absent in most families.
Several syndromes, chromosomal aberrations and congenital
abnormalities are commonly reported in Wilms tumor.
WAGR syndrome


Wilms Tumor
Aniridia
Genitourinary malformation
Mental retardation
(Constitutional deletion of
chromosome 11p13 )
Beckwith-Wiedmann syndrome
Hemihypertrophy
Visceromegaly
Macroglossia
Hypoglycemia
3-5% risk of
developing Wilms
tumor
Variety of 11p15.5
abnormalities have
been reported with
this syndrome

Denys-Drash syndrome
Male pseudohermaphordism
Early-onset renal failure and nephrotic syndrome
characterized by mesangial sclerosis
Increased risk of Wilms tumor
Typically patients with this syndrome carry point
mutation within the WTI gene.
Other conditions with increased risk of Wilms
tumor: Sotos syndrome, Neurofibromatosis, von
Willebrand disease
Clinical Manifestations:
Abdominal mass, usually incidental finding,
variable in size, smooth and firm
Abdominal pain and vomiting
Hematuria
Hypertension probably due to renal ischemia
Occasionally, rapid abdominal enlargement and
anemia due to bleeding into renal parenchyma or
pelvis

Diagnosis:
Any abdominal mass must
be considered malignant
until proved otherwise
CT/MRI confirm:
Intrarenal origin, extent of
tumor, involvement of IVC
and integrity of the other
kidney.
Chest CT scan can identify
metastases not seen on
plain radiograph.
CBC, KFT, LFT

Treatment:
Surgical resection with inspection of of patency of
IVC, the other kidney &the liver for and
retroperitoneal L.N for metastases
Chemotherapy: Most centers utilize it and the
choice depends on the stage and histology.
Radiotherapy is also administered to the tumor
bed
For bilateral Wilms, chemotherapy plus unilateral
nephrectomy and contralateral partial
nephrectomy or bilateral partial nephrectomy