Pediatric Oncology
March 4, 2011
Dr Cynthia Castro
b.
According to Dra Castro, she will be taking her exam from the lecture and read on Germ
Cell Tumor from Nelson’s (which we have included in this trans)
This trans seems long but it’s not as tough to understand as you will see.
LEGEND:
Normal text – Lecture and ppt
Italicized with  bullet – from audio
Italicized with  bullet – Nelson’s Textbook of Pediatrics (for the Germ Cell
Tumors)
OUTLINE
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.
XIII.
Introduction
Causes of Childhood Cancer
Risk Factors
Abnormal Response to Infection
Warning signs of cancer in adults and children
Cancer Diagnosis
Leukemias
Lymphomas
Neuroblastoma
Nephroblastoma
Rhabdomyosarcoma
Bone Sarcoma
Germ Cell Tumors
INTRODUCTION
 A proliferation of cells whose unique trait—loss of normal controls—
results in unregulated growth, lack of differentiation, local tissue
invasion, and metastasis.
 STATISTICS
 Worldwide,
 46 children get diagnosed with CA everyday
 1/330 children would be diagnosed by the time they reach
the age of 20;
 4000 die of CA each year = 11 children every single day, every
single year
 Cancer in childhood occurs in regularly, randomly and spares
no ethnic group, socioeconomic class or geographic region
 More children die from cancer each year than cystic fibrosis,
AIDS, and genetic anomalies






Leading causes of morbidity and mortality in PHIL
1. Communicable diseases
2. Cardiovascular diseases
3. CANCER
75% occurs after age 50
3% occurs 14 years and below.
It is estimated that for every 1800 Filipinos, 1 develop CA
annually
50,000 per year of 90M
Every two new CA cases annually, one will die within the year.
CAUSES OF CHILDHOOD CANCER
 Largely unknown Etiology
 Incidence at early age and cell type of origin suggest that causative
factors operate before birth and possibly even before conception.
 It is interplay among genetic, environmental and constitutional factors
Genetic Susceptibility
 Cancer is the result of multiple mutations in the DNA of a cell.
 Mutations
 DNA is highly conserved, sometimes protein transcriptions goes
haywire but supposedly if the body is immunocompetent, it can
remove the mutation by:
1. APOPTOSIS/ programmed cell death
2. IMMUNE SYSTEM: if the cell escapes apoptosis, the
immune system will recognize abnormal cell as
foreign such as NK, helper and cytotoxic T cells.
TYPES OF MUTATIONS
a.
Inherited- genetic alteration has been passed on to the child
from a parent present in the egg or sperm before
fertilization
Acquired- DNA changes acquired during a person’s life
(lifestyle)
KNUDSON’S 2-HIT THEORY OF CANCER CAUSATION
- The theory states that two hits are necessary for cancer. One hit
must disable each copy of the tumor supressor gene, one on each
chromosome
- People with a hereditary susceptibility to cancer inherit a damaged
gene on one chromosome, so their first hit occurs at conception
- So another hit on the remaining good chromosome would make the
cell produce cancer
- Ex. Retinoblastoma, people who inherit the first hit are (100, 000 x)
more likely to develop a second cancer causing mutation
 Mutations from parents may be passed on to the child (first hit).
The second hit is most often due to environmental or lifestyle
factors (smoking, alcohol, obesity, HTN, exposure to carcinogens).
This predisposes to the development of cancer
 Mutations may occur in the cell of the child (and not inherited
from the parents). The second hit may occur either by inheritance
of a cancer gene or a cancer predispostiion from parents and/or
environmental or lifestyle factors.
Environmental causes of cancer
- everywhere we read: exposure to TV radiation, radio waves or
electromagnetic fields, smoking, insecticides, even CELLULAR phones are
implicated in Brain Cas, even microwaves and computers; ULTRAVIOLET
WAVES though have had positive feedback in studies especially among
caucasians.
RISK FACTORS
TV exposure, electromagnetic field, smoking, insecticides,
cellphones (implicated in some brain tumors), sound waves, UV
radiation, microwave, laptops.
 For children, the most common risk factors are: viruses, genetic
diseases, exposure to previous chemotherapy, mutation, ionizing
radiation
1. Ionizing Radiation
o
High levels of ionizing radiation from accidents or from
radiotherapy have been linked with increased risk of some
childhood cancers

2. Chemotherapy and Radiotherapy
o
Children treated with chemotherapy and/or radiotherapy
have an increased risk of developing a second primary
cancer.
o
Because of the treatment you are predisposed
o
Survivors of Primary Cancer have a 3-6 fold increase risk of
second malignancy compared to general population with a
latency period of 5 – 10 years
 Cancer that develops due to treatment of another cancer
 i. e. Children treated with Rhabdomyosarcoma develops
myeloid leukemia in 6 – 10 years.
3. AIDS
o
Children with AIDS have an increased risk of
NHL, Kaposi’s sarcoma, and leiomyosarcoma.
developing
4. Genetic Syndrome
o
Certain
genetic
syndromes
(Li-Fraumeni
and
neurofibromatosis) have an increased risk of specific
cancers.
 Li – Fraumeni is a condition in which patients develops
multiple cancer due to mutation of p53, the guardian of the
genome.
o
Syndrome
will predispose one to multiple cancers,
simultaneously even for the latter
5. Down Syndrome
o
20-fold increased risk of developing leukemia.
 some patients present with very high WBC count, then on
further workup, they are discovered to have Down syndrome that
was not physically apparent
 For these children, sometimes if you just observe, the abnormal
cells disappear, called Transient Myeloproliferative Syndrome (still
they have 40% chance of developing trans – leukemia later;
usually before 6 years old)
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6. Obstetric Procedures
o
Increased risk of childhood cancer associated with antenatal
obstetric irradiation was discovered over 40 years ago.
o
Obstetric x-ray examination in pregnancy has been largely
superseded by ultrasound examination. (3D 4D ultrasound)
7. Infectious Agents
Virus/Organism
Cancer
Helicobacter Pylori
Gastric Cancer
HIV
Non-Hodgkins lymphoma, Kaposi’s sarcoma,
squamous cell carcinomas
Hepa B & C
Liver Cancer
Schistosomiasis
Bladder Cancer
EBV
Burkitt’s Lymphoma
HPV
Cervical and Anal Cancer
8. Infections and ALL
o
high incidence in affluent western population
o
lower incidence in socio-economically disadvantaged groups
and less developed countries
o
ALL could be associated with an infectious agent linked to
public hygiene conditions.
o
Childhood acute lymphoblastic leukemia is associated with
an infectious agent linked to hygiene conditions.
 exposure to infectious agents poses challenge to the immune
system which becomes more “trained” in fighting these agents
and also cancer cells
ABNORMAL RESPONSE TO INFECTION
1.
2.
Delayed Infection Hypothesis
o
ALL can result from lack of exposure to infection and
consequent failure of immune system modulation during
infancy.
o
Children with ALL tend to have had relatively few infections
in the first months of life, fewer immunizations in infancy
and a shorter period of breastfeeding, and are more likely to
be first born or only child.
Impaired Herd Immunity
o
Leukemia is a rare response to a common infection in
particularly susceptible children
o
Siblings of children diagnosed
with
leukemia,
Hodgkins Lymphoma, Wilms tumor neuroblastoma, bone
tumors,
the risk for same cancer is 1.5x greater than
in race and gender matched controls.
Can Childhood Cancers be prevented?
** ACS state that although many adult cancers can be
prevented by lifestyle alterations such as exercise, diet,
less alcohol & smoking, there is no known way of
preventing most childhood cancers.
Can Chilhood cancer be found??
** Childhood CA are often hard to recognize. Most childhood
CA SSX mimic those of other illnesses thus the dismissal,
e.g. bone pains – baka naman growing pains lang ‘yan.
One will find it difficult to differentiate this from or
suspect, at the very least, bone malignancy. Growing
pains like in teething are very usual.
** A high index of suspicion is needed for CA to be suspected.
The reluctance to suggest a malignat differential among
pediatricians is usual because of the ominous implication
** Reluctance to suggest a diagnosis for the primary care
physician and the family
Often, it takes months after the onset of first
symptom (average of 100-230 days) before the DX
of CA so parents are implored to regularize checkups and monitor and report any additional signs and
symptoms that do not go away
Lag Time in the Diagnosis of certain cancers of Children
Diagnosis
Days
Hodgkin’s
223
Brain
211
Ewings
182
Ostesarcoma
127
Rhabdomysarcoma
127
Neuroblastoma
120
Leukemia
Wilm’s tumor
109
101
This table means that many of the cancers in children are diagnosed late.
This maybe because the parents usually does not think of cancers when they
see signs, and that often, they do not know the signs. For instance, Brain
tumors are diagnosed 211 days later.
 As medical practitioners, you should inform the mother to bring her
children for consult for symptoms that do not go away.
WARNING SIGNS OF CANCER IN ADULTS AND CHILDREN
CAUTION: Among Adults/ warning signs

Change in bowel or bladder habits

A sore that does not heal

Unusual bleeding or discharge

Thickening or lump in the breasts or elsewhere

Ingestion of Difficulty swallowing

Obvious change in wart or mole

Nagging cough or hoarseness

… with associated pain, anorexia & weight loss
Warning Signs of Cancer in Children

Continued or unexplained weight loss

Headaches with vomiting in the morning

Increased of swelling or persistent pain in bone and joint

Lumps in the abdomen or neck or elsewhere

Development of whitish spot in the pupil

Recurrent Fever not associated to infection

Excessive bruising or bleeding

Noticeable paleness or prolonged tiredness
1. Continued and Unexplained Weight Loss
- Children don’t normally lose weight over long periods of time
- They might lose a pound or two with an acute illness but should
quickly gain it back
- Loss of body mass that cannot be reversed nutritionally
- Involuntary weight loss of >5% of pre morbid weight occurring within
a 6 month period
- Nutritional assessment: anthropometric measurements, skin fold
thickness, mid arm circumference
2. Headaches with Vomiting in the Morning
- Pediatric brain tumors are frequently situated so that they interfere
with CSF circulation, and increased ICP is a common occurrence.
Lesions
Supratentorial
Infratentorial
Ask For











Vomiting
Headache
64%
76%
43%
56%
Coordination
difficulties
NA
59%
History
Duration of symptoms
Location
Timing
Severity
Precipitating event
Mode of onset
Recurrent morning headache
Headache that awakens the child
Intense and incapacitating headache
Changes in the quality, frequency, and pattern of the headaches
Diagnostic Tests
•
CT or MRI
•
Best method of screening for a brain tumor in a patient with
headache is a careful neurological exam
•
95% of children with headaches and brain tumor have abnormal
neurological findings
3. Increased Swelling or Persistent Pain in Bone and Joint
Leukemia: 27-33%
Primary bone cancers
o
Osteogenic sarcoma: 79%
o
Ewing’s tumor: 89%
Metastatic diseases to bone or bone marrow
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-
Does not follow a known injury
Does not improve in a few weeks
Different from “Growing pains”
o
Occurs at night
o
Does not cause pain in a specific spot
o
Helped by massage
o
Does not limit the child’s activity
o
Does not tend to be chronic
4. Lump or Mass in Abdomen, Neck and Elsewhere
a. Abdomen
- Newborns: renal (Wilms’ vs neuroblastoma)
- Older children: involvement of liver or spleen in leukemia or
lymphoma
- PE: Structures palpable in a normal child: liver edge, spleen,
kidneys, aorta, sigmoid colon, feces, spine
b. Lymph nodes
- Rapidly increase in size during the first 12 years of the child’s
life
- Enlarged
>10mm in greatest diameter
5mm epitrochlear
>15mm inguinal
Indications for Lymph Node Biopsy
•
An enlarging node or nodes that remain enlarged after 2 to 3
weeks of antibiotic therapy
•
Nodes that are not enlarging but have not diminished in size
after 5 to 6 weeks, especially if associated with unexplained fever,
weight loss or hepatosplenomegaly
c. Thoracic Mass
Mediastinum
o
Anterior: lymphoma, teratoma, thymus and thyroid
tumors
o
Middle: lymphoma, bronchogenic cysts
o
Posterior: neuroblastoma, other neurogenic tumors
5. Development of a Whitish Appearance in the Pupil of the Eye
- Retinoblastoma is fairly common in the RP (1/18000 live
births) and wtih present with leukocoria  abnormal white
pupillary reflex/ reflection from the retina of the eye,
resembling eyeshine. Cat’s eyes.
- Sometimes with strabismus
- Inflamed eye/orbit
 always obtain look at the ROR of children. For those born at
home, their mothers always complain that their children have
cat’s eye.
6. Recurrent Fevers Not Caused by Infections
- FUO T > 38.3°C of >3 weeks
- Blood, liver, brain, kidney
- 2.3% risk
7. Excessive Bruising and Bleeding
- Easily noticed by parents so never missed
- Straight to work-up like CBC
8. Noticeable Paleness or Prolonged Tiredness
Anemia
o
Exogenous blood loss
o
Intratumoral bleeding
o
Erythrophagocytosis
o
Bone marrow replacement

Neuroblastoma

Lymphoma

Ewing’s tumor

Rhabdomyosarcoma
CANCER DIAGNOSIS
Optimal therapy can begin only after the tumor has been accurately
diagnosed and the extent of the disease precisely defined
•
Non-invasive imaging techniques
•
Tumor markers
•
Pathologic confirmation
Diagnostic Methods for Tumor Diagnosis
 Light microscopy
 Immunohistochemistry
 If Histopath was done with the result of “ round blue cell tumors”
(etiology discussed later), these may be cause by different
etiology→submit for immunohistochemistry (however, they get more
and more expensive as you order more specific tests. Tailor the tests to
what the patient’s family can afford)
 Molecular genetic: RT-PCR
 Molecular genetic: FISH
 FISH is Fluorescence in situ hybridization (used in CML to identify abl –
bcr gene)
 Special stains
 For leukemia, some of the special stains used are myelopeoxidase and
non – specific esterase
 Electron microscopy
 Cytogenetics
Staging

Provides information on prognosis and guides treatment selection

Tests involved in clinical staging: X-rays, computed tomography (CT
scans), magnetic resonance imaging (MRI), ultrasounds, bone
marrow biopsies, bone scans, lumbar puncture, etc
TNM STAGING CLASSIFICATION
T= Extent of primary tumor (1-4)
N= Presence or absence and extent of regional lymph node metastasis (0 to
3)
M = Presence or absence of Metastases (0 or 1)
Numerical value is assigned to each letter to indicate size or extent of disease
Numerical stages
a.
Stage 0 – Carcinoma in situ
b. Stage I – localized tumor
c.
Stages II & III – local and regional extension
d. Stage IV – distant metastases
Distribution of Childhood Cancer
CA
CA
CNS
17%
HD
ALL
16%
NHL
11%
8%
CA
AML
5%
LEUKEMIA


A malignant, clonal proliferation of hematopoietic cells
The most common among childhood malignancies
 also CNS tumors are common, but leukemia remains the one
with the highest incidence
Classification of Leukemias  cell type, not duration

Acute – clonal expansion of immature hematopoietic precursors
– there is proliferation of blast cells

Chronic – clonal expansion of mature marrow elements
– there is failure of apoptosis

Congenital – diagnosed within the first 4 weeks of life
ACUTE LEUKEMIAS
 Proliferation of blast cells (immature cells)
 vs. Chronic Leukemias (proliferation of mature cells with increased lifespan
due to deficient apoptosis)
 AUL – Acute Undifferentiated Leukemia
 AMLL – Acute Myelolymphocytic Leukemia (mixed blast and mature cells)
Epidemiology

97% of all childhood leukemias
o
ALL – 75%; AML – 20%; AUL – < 0.5%

Peak incidence: 2 – 5 years old
 this is the best time to have leukemia because patient’s age is a
risk factor for prognosis of leukemia. The younger the child, the
better the prognosis.

M:F = 1.1:1 - 1.4:1

Highest rates among Hispanics, Filipinos and Chinese, lowest
among African Americans
Genetic Risk Factors

Down syndrome
o
20-fold increase in risk

Neurofibromatosis type 1

Ataxia telangiectasia

Bloom syndrome

Fanconi anemia
Transient myeloid proliferation syndrome
o
Similar to leukemia but self-limited (in Down’s Syndrome)
o
25% eventually develop frank AML
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Clinical manifestations

Fever  caused by cytokines secreted by lymphoblasts
Also patients with leukemia have abnormal WBC count, thus
prone to infection→fever

Pallor
 due to anemia

Bruising

Petechiae
Bruising and petechiae due to thrombocytopenia

Bone pain  due to increased multiplication of marrow elements

Limping gait

Hepatosplenomegaly

Lymphadenopathy
Differential diagnosis
 Idiopathic thrombocytopenic purpura
 usually presents with ISOLATED THROMBOCYTOPENIA; they do not
present with anemia or abnormal WBC (but leukemia do)
 Aplastic anemia
 Does not present with lymphadenopathy or hepatosplenomegaly (but
leukemia do)
 However, PANCYTOPENIA presents with organomegaly and
lymphadenopathy. These symptoms are suggestive of leukemia unless
proven otherwise
 Juvenile rheumatoid arthritis (JRA)
 Now more commonly called JIA (Juvenile Idiopathic Arthritis); presents
with anemia
 Connective tissue disease (e.g. SLE)
 Infectious mononucleosis  enlarged lymph nodes
 presents with lymphadenopathy, lymphocytic predominance
 Neuroblastoma  can also invade the bone marrow, thus causing the
signs and symptoms
 May invade the bone marrow to cause the same signs and symptoms as
leukemia
Complete Blood Count
 (+) anemia
o normochromic, normocytic
 Abnormal leukocyte count and differential
 Note that the differential count of children 4 years old and below has
LYMPHOCYTIC PREDOMINANCE, which you may mistakenly consider for
leukemia.
 After 4 years old, this usually reverses to the adult type of
NEUTROPHILIC PREDOMINANCE
 (+) blasts
 important to look at the PBS
 Thrombocytopenia
o low platelet count  bruising, bleeding
** Pancytopenia without organomegaly = APLASTIC ANEMIA unless
proven otherwise
** Pancytopenia with hepatosplenomegaly = LEUKEMIA unless proven
otherwise
 Take note of this table. (We will show you the AML classification later)
Diagnostic Procedures

Morphology
o
Lymphoblasts are more dense in appearance and do
not contain nucleoli.
o
Myeloblasts contain nucleoli and have adequate to
moderate amounts of cytoplasm.
FRENCH AMERICAN BRITISH CLASSIFICATION
(FAB CLASSIFICATION)
o
AML FAB Classification:
M0
Undifferentiated leukemia
M1
AML w/o maturation
M2
AML w/ maturation
M3
Acute promyelocytic leukemia (APL)
 Curable with VIT E (RETINOIC ACID) which pushes the
myelocytes to differentiate.
 Presence of AUER RODS
M4
Myelomonocytic leukemia
M5
Monocytic leukemia
 Can also present the same way as ALL
M6
Erythroleukemia (di Guglielmo syndrome)
M7
Megakaryocytic leukemia
In this table, pay attention to M3. Generally, AML is difficult to treat. They
usually require Bone Marrow Transplants. ALL on the other hand requires
chemotherapy alone. M3 IS AN EXCEPTION. M3 (APL – acute promyelocytic
leukemia) is curable with Vitamin E (retinoic acid).
The role of vitamin E in the treatment of M3:
M3 or acute promyelocytic leukemia is very near the next stage (myelocytic
stage) in terms of differentiation. The vitamin E induces the M3 to
differentiate to the Myelocytic forms, thus the abnormal cells become
omitted. This is of course best achieve with concomitant chemotherapy.
Look at M3. It has many granules. When these granules coalesce, they
form the AUER RODS.

Cytochemistry ( remember these)
o
ALL:
(+) Periodic acid Schiff (PAS)
o
AML:
(+) Myeloperoxidase (MPO)
(+) Sudan black
(+) Specific and non-specific esterases

Flow cytometry (Immunophenotyping)
o
ALL:
B cell  CD 19, CD 20
Pre B cell  CD 10 (common ALL antigen/CALLA)
T cell  CD 3, CD 5, CD 7
 A lymphocytic leukemia cell with low CD (cluster of
differentiation) is most probably a T – cell.
 Higher CD: B – cell
 Pre – B: only CD 10 or the presence of CALLA
(common acute lymphocytic leukemia antigen)
 Mixed/Biphenotypic cells may present with any CD
number
o
AML:
CD 13, CD 33
** Different subtypes = different
chemotherapeutic protocols**
Peripheral Blood Smear
Lymphocytes have no cytoplasm
Nuclei have loose chromatin material
Indications for Bone Marrow Aspiration (BMA)
- Finding of atypical or blast cells on PBS
 Do BMA if there are SSx suggestive of leukemia plus abnormal PBS
- Significant depression of >1 peripheral blood cell element w/o obvious
explanation
- Association w/ unexplained lymphadenopathy or hepatosplenomegaly,
or a thymic mass
- Absence of an infectious cause for the blood abnormality
 the normal BMA result shows heterogenous population of cells (small,
big, dark, light cells)
 the typical BMA result of acute leukemia shows HOMOGENOUS
population of leukemic blast cells
Bone Marrow Smears

Normal bone marrow: heterogenous cell population

Acute leukemia: only one, monotonous cell population
Acute Lymphoblastic
Acute Myelogenous
vs
Leukemia
Leukemia
(+)
Hepatosplenomegaly
(-)
(+)
Lymphadenopathy
(-)
(+)
CNS Leukemia
(-)
** All 3 are found in ALL and absent in AML except for monocytic leukemia
(AML M5 classification) which also presents with these symptoms. **
ALL: FAB L1
FAB L2 usually mistaken as myeloid
FAB L3  has prominent cytoplasmic vacuolization
Cytochemistry costs P3,000 – P5,000, Flowcytometry costs P1,500
Tailor the cost to what your patient can afford.

Cytogenetics
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Different subtypes of leukemia (as in different CD’s or different
FAB classification for AML) would require different treatment protocol and
would have different prognosis.
Phases of Therapy

Remission induction
o
Aim is to remove all the abnormal cells but it does not
stop there since the cells that are removed are only
the ones in the bone marrow

Consolidation therapy

Intensification therapy

CNS treatment

Continuation therapy (around 3 years of treatment)
Note that the basis of all drug treatment protocol for cancer treatment in
children is ALL because many children have ALL and this leukemia has good
response to treatment and so follow up is easy for this patient. This means
that if a drug company is to test for the effect of a particular drug for
leukemia, they will test it to patients with ALL (not AML) due to reasons
stated above and the results are just translated to other malignancy.
Treatment
ALL
Vincristine
L- asparaginase
6 mercaptopurine
Methotrexate
Intrathecal MTX
AML
Anthracycline (Idarubicin, Doxorubicin,
Mitoxantrone)
Cytosine arabinoside
Intrathecal Methotrexate (MTX) for M5
All trans Retinoic Acid (ATRA) for M3
Bone Marrow Transplant ( bone
marrow transplant is employed in AML for
patients who relapse)
o
Produces p210 protein, a tyrosine kinase that makes
cells resistant to apoptosis
Signs and Symptoms

Mostly asymptomatic (>50%)
so most of CML are diagnosed during annual PE

Pallor

Fever

Easy bruisability

Splenomegaly

Priapism – a persistent and painful erection () due to increased
WBC concentration in the penis. Painful and may lead to
amputation due to decreased blood supply.
(hehe kung saan – saan nakasingit ung audio)
Laboratory Tests
 CBC
o
leukocytosis and basophilia
 Leukocyte alkaline phosphatase activity (LAP score)
o
Low or Zero

Differentiate it from leukocytosis due to
infection which has a high score
 Clinical Use of the LAP score:
If a patient suspected of leukemia has fever and you suspect the
increased WBC is due to fever, do LAP score.
LAP score of AML is very low to zero hile that of reactive
leukocytosis due to infection will have high LAP score.
 Bone marrow aspiration (BMA)
o
granulocytic hyperplasia () which looks like this:
 A new protocol recently added in the treatment of AML is ETOPOSIDE.
Sanctuary Sites: CNS, Testes, Eye
 these are the sites that are difficult to penetrate via chemotherapeutic
drugs. The technique employed is usually direct intrathecal therapy.
CNS Leukemia

On lumbar tap  > 5 WBC/mm3

(+) blast in cytospin
o
CNS 1: <5 WBC, no blast in cytospin
o
CNS 2: <5 WBC, (+) blast on cytospin
o
CNS 3: >5 WBC, (+) blast on cytospin
 CNS leukemia is treated with chemotherapy
 AML and Monocytic Leukemia (AML M5 in FAB classification) are also
treated with chemotherapy. If not, they will develop CNS leukemia in 7 – 10%.
Prognostic factors

Age
o
1 – 9 years old  best prognosis

Leukocyte count
o
< 50,000  better prognosis
o
> 100,000  high risk leukemia ( chance of cure
maybe achieved by intensive chemotherapy)

Immunophenotype

Chromosomal abnormalities

Overt CNS disease at diagnosis

Early response to induction chemotherapy

Minimal residual disease at end of treatment
Prognosis

ALL with chemotherapy
o
90% complete remission rate
o
75% cure rate
o
7-8/10 achieve cure

AML
o
Never claim cure rate unless given bone marrow
transplant
o
40% 4 yr Disease-free Survival with chemo
o
50% 4 yr DFS with BMT
 ALL is easy to treat, so wh can achieve cure rate. For AML, we usually
cannot talk about cure rate but only DFS (disease free survival) because it is
difficult to treat.


Chronic Myelogenous Leukemia
<5% of all childhood leukemias
 most common of the chronic leukemias
Cytogenetic hallmark is the Philadelphia chromosome
o
Translocation between chromosomes 9 and 22: t(9;22)
o
Demonstrates BCR-ABL gene rearrangement
the abl comes from chromosome 9 while bcr comes
from chromosome 22)
 Karyotyping
o
Philadelphia chromosome () which looks like this:
The above portion (green) of the Philadelphia
chromosome is the abl that was cleaved from
chromosome nine, while the lower (orange) portion of
this chromosome comes from chromosome 22.
Philadelphia therefore is a small chromosome.
 Fluorescence in situ hybridization (FISH)
o
BCR-ABL gene
 FISH identifies the presence of abl – bcr gene by way of
fluorescens (lighting them up; they appear glow in the dark)
Differential Diagnosis

Leukemoid reaction
o
WBC count of >50,000

Juvenile Myelomonocytic Leukemia (JMML)
o
Fetal haemoglobin is very high

Other myeloproliferative disorders
Treatment

Cytoreduction
o Hydroxyurea, Busulfan, Leukapheresis

Interferon alpha (2a, 2b and n1 variants) – () ablates the
Philadelphia chromosome.

Tyrosine kinase inhibitor
o Oral Imatinib Mesylate

Expensive but can really cure!
 Imatinib blocks the normal binding site of
ATP that activates Tyrosine kinase. Without
the activation of the latter, no downstream
signal for proliferation is sent to the
nucleus.
 1 tablet costs P200. Has to be given at 4
tablets a day everyday. P5,600 per week.
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
Bone marrow transplantation
 requires a suitable donor
 for 10 – kg child, BM transplant costs P3 MILLION. The older
the child, the heavier, the more expensive!!!
Phases
Median duration
WBC
Blasts
Basophils
Platelets
Chronic
5-6 years
> 20,000
0%
Increased
Increased or
normal
Accelerated
6-9 months
> 10%
> 20%
Increased or
decreased
Blastic
3-6 months
> 30%
Decreased
 Typically present as Stage I and progresses slowly
Nodular Sclerosis
 30-60% incidence
 Mediastinal involvement common
 Microscopically presents with nodular appearance with variable RS
cells
 Good prognosis, usually present at early stage of disease
Mixed Cellularity
 20-40% incidence
 Microscopically presents with numerous lymphocytes, plasma cells,
eosinophils and RS cells
 Intermediate prognosis with good response to therapy
 For this table, note that majority of patients are diagnosed in chronic
phase.
 If no treatment, patients will remain in the chronic state for 5 -6 years
 in the accelerated phase, there is increase blast cells. If given
chemotherapy, they will go back to the chronic phase, though some don’t.
These patients who do not revert back to chronic phase progresses to the
Blastic phase (which is acute leukemia phase: either AML or ALL)
LYMPHOMA
 Lymphoma can present in any location where normal lymphocytes
are found
 Not one but a group of cancers that arise when lymphocytes
become malignant
 Lymphoma cells either grow too fast or fail to die, thus forming
tumors in the body, most commonly in the lymphatic system
 Can either be Hodgkin’s or Non-Hodgkin’s
HODGKIN’S LYMPHOMA
 Progressive enlargement of the lymph nodes
 Unicentric in origin
 Clinically, it has a PREDICTABLE PATTERN of spread (important
difference from Non-Hodgkin’s Lymphoma) by extension to
contiguous nodes ( growth to contiguous nodes so the nodes
involved are close to each other.
Involved nodes in Non – hodgkin’s lymphoma are separated in
space.)
 15% of all lymphomas
 Cause not really known but infections and abnormal immunologic
response are suggested
 Bimodal incidence/ biphasic
- First peak during 15-35 years
- Second peak after the age of 50
 Sex ratio in children: 3:1 (M:F)
 Increased incidence among consanguinous family members and
among siblings
 Immunologic disorders: SLE, RA, ataxia telangiectasia, Swiss-type
agammaglobulinemia
 Highly associated with EBV
 HL is a malignant tumor in which Reed-Sternberg (RS) cells are
present in a reactive background
Reed-Sternberg Cell:
 A large/GIANT cell (15–45 μm in
diameter) with multiple or
multilobulated nuclei
 “Owl’s eyes”
 Considered the hallmark of HL
 Clonal in origin and arises from the
germinal center B cells
Forms of Hodgkin’s Disease
• Childhood: < 14 years of age
• Young adult:15-34 years of age
• Older adult: 55-74 years of age
REAL CLASSIFICATION
 Lymphocyte predominant, nodular (with or without diffuse areas)

Classic Hodgkin’s Disease
Lymphocyte-rich classic disease
Nodular sclerosis
Mixed cellularity
Lymphocyte depletion
Lymphocyte Depleted
 Common in patients with HIV infection
 Worst prognosis presenting as Stage III or IV
 Microscopically presents with numerous pleiomorphic mononuclear
and RS cells, fibrosis, and very few lymphocytes
 Refractory to therapy
Clinical Presentation:
 Lymphadenopathy
- PAINLESS, firm, rubbery cervical or supraclavicular lymph nodes
- If seen on the RIGHT = drained from the LUNGS
- If seen on the LEFT = drained from the ABDOMEN
 Widened mediastinum on Chest X-Ray
- Due to lymph node involvement in the mediastinum
 Extranodal involvement
- Liver (hepatocellular dysfunction), Spleen, Bone marrow
infiltration, airway obstruction, pleural or pericardial effusion
 Nephrotic syndrome
 B symptoms (MORE PROMINENT in Hodgkin’s than in NonHodgkin’s)
- CYTOKINES are responsible for the B symptoms

IL-1 and IL-2: Unexplained fever and night sweats

Tumor Necrosis Factor: weight loss

Transforming growth factor B: proliferation of Reed
Sternberg Cell and immunosuppresion
 Other symptoms: Pruritus, Lethargy, Anorexia ,Alcohol-induced pain
Differential Diagnosis:
always TB vs Lymphoma
 Tuberculosis (the great mimic)
 Toxoplasmosis
- Because of the lymphadenopathy
 Non-Hodgkin’s lymphoma
 Metastatic cancer
Diagnostic Evaluation:
 Excisional Biopsy
- Warranted for a growing lymph node that is present for > 6
weeks with (-) PTB titers
 Immunophenotypic Markers
- Anaplastic (Ki-1) Lymphoma: there is skin involvement
 PE with measurement of lymph nodes
 CBC, ESR, renal and hepatic function tests, alkaline phosphatase
 Lymph node biopsy
warranted if lymph node present for more than 4 weeks,
growing, (-) TB, (-) Infectious mononucleosis
 CXR with measurement of mediastinal ratio
 Chest and neck CT scan
 CT scan or MRI of abdomen and pelvis
 Lymphangiogram
 Bone marrow biopsy
 Bone scan (sometimes done)
 Gallium scan
 Surgical staging with lymph node sampling
ANN ARBOR STAGING CLASSIFICATION
I
Single lymph node involvement
II
2 or more lymph nodes but on the same side of the diaphragm
III
2 or more lymph nodes on both sides of the diaphragm, spleen
included
IV
With involvement outside the lymphatic system (bone
marrow, liver, extranodal sites)
RYE CLASSIFICATION SYSTEM
Lymphocyte Predominant
 <10% incidence
 Microscopically presents with numerous small lymphocytes with few
classic RS cells
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








Risk Groups

Favorable: Stage I and IIA

Intermediate: IIB and IIIA

Unfavorable: IIIB and IV
Treatment:
 Multiagent chemotherapy (MOPP, ABVD)
- ABVD: doxorubicin [Adriamycin], bleomycin, vinblastine and
dacarbazine
- MOPP: mustargen, [Mechlorethamine], oncovin [Vincristine],
procarbazine, prednisone
 Combined-modality treatment with radiotherapy
- Done if multiagent chemotherapy fails
- Avoided since it can affect the bone marrow and growth of the
patient
Prognosis
 Treated with curative intent
 Over all cure rate
- > 90% with early stage
- > 70% with advanced stage (use combined multiagent
chemotherapy)
 10-20% with advanced stage
- may relapse
 Malignant clonal proliferation of lymphocytes of T-, B-, or
indeterminate cell origin
 Pattern of spread is not contiguous and could arise anywhere.
 85% of malignant Lymphomas
 Lymph nodes, Peyer’s patches, spleen
 Bone marrow in children
 Rare: bone and primary CNS
 B Symptoms relatively uncommon
NHL Incidence and Epidemiology
• 45% of all lymphomas in children and adolescents < 20 years old
• Isolated cases of familial NHL occur
• M:F 2.5:1
• Peaks at 15-19
NHL Risk Factors
• Genetic
- Immunologic defects (agammaglobulinemia, ataxia
telangiectasia, WAS, SCID)
• Post transplant immunosuppression
• Drugs: diphenylhydantoin
• Radiation
• Viral: EBV, HIV
WHO Classification of NHL
• Precursor B-cell neoplasms
• Mature (peripheral) B-cell neoplasms
• Precursor T-cell neoplasms
• Mature (peripheral) T-cell neoplasms
Clinical Manifestations
• Lymphoblastic
- Mediastinal mass, SVC syndrome, lymphadenopathies, bone, BM,
testis, skin, CNS
• Small non-cleaved cell lymphoma (SNCCL)
- abdominal tumors
- LCC (large Cell)
- occur in many sites: abdomen, mediastinum, skin, bone, soft
tissues, CNS very rare
Diagnostic Evaluation:
 CBC
Serum electrolytes, uric acid, LDH, creatinine, calcium, phosphorus
Liver function tests
CXR and chest CT if abnormal
Abdominal and pelvic US and/or CT
Gallium scan and/or bone scan
Bilateral BMA and biopsy
CSF cytology
Lumbar tap
ONLY the HISTOPATHOLOGY and the IMMUNO-HISTO-CHEMISTRY
will tell you if it’s Hodgkin’s or Non-Hodgkin’s
ST. JUDE STAGING SYSTEM FOR CHILDHOOD NHL
I
A single tumor (extranodal) or single anatomic area (nodal), with
the exclusion of mediastinum or abdomen
II
A single tumor (extranodal) with regional node involvement
Two or more nodal areas on the same side of the diaphragm
Two single (extranodal) tumors with or without regional node
involvement on the same side of the diaphragm
A primary gastrointestinal tract tumor with or without involvement
of associated mesenteric nodes , which must be grossly (>90%)
resected
III Two single tumors (extranodal) on opposite sides of the
diaphragm
Two or more nodal areas above and below the diaphragm
Any primary intrathoracic tumor (mediastinal, pleural, or thymic)
Any extensive primary intra-abdominal disease
All primary paraspinal or epidural tumors regardless of other sites
IV Any of the above, with initial involvement of central nervous
system or bone marrow at time of diagnosis (disseminated
disease)
Treatment:
 Multiagent chemotherapy: (COMP, CHOP)
- COMP: cyclophosphamide, vincristine, methotrexate, 6mercaptopurine and prednisone
- CHOP: Cyclophosphamide, hydroxydaunorubicin [Doxorubicin],
oncovin [Vincristine] and prednisone
Prognosis
• Early stage (I/II): 90% of cases are cured
NON HODGKIN’S LYMPHOMA
• Advanced stage (III/IV):
SNCCL: 90% survival in localized disease
70-80% in disseminated disease
LCL: 50-70%survival rate T cell
95% 6 yr event free survival B cell
NEUROBLASTOMA
 Embryonal cancer of the peripheral sympathetic nervous system
- Seen along the spine, pineal gland and adrenal gland
 Most common extracranial solid tumor in children (8-10% of all
childhood cancer)
 Most common cancer diagnosed in infancy
 Median age at diagnosis: 2 years old
 90% of cases diagnosed before age 5
 More common in boys that in girls
 Short arm of Chromosome 1p36 is a frequent site of somatic
deletion in neuroblastoma cells
Clinical Presentation:
 Can arise from any site along the sympathetic nervous system chain
 Abdominal in origin: 65% of cases
 Adrenal in origin
- 40% of cases in older children
- 25% of cases in infants
 Primary tumor cannot be found in 1% of cases
- Urine test can be done: Check for VANILLYLMANDELIC ACID
(VMA) and HOMOVANILLIC ACID (HVA)
- Elevated levels means that it’s most probably a Neuroblastoma
 Majority are diagnosed by age 5 and becomes rare after age 10
 Calcifications and Hemorrhages are common
Signs and Symptoms:
 Fixed hard abdominal mass
 Horner syndrome (ptosis, miosis, enophthalmos, anhidrosis): if
location is in the superior cervical ganglion
 Cervical lymphadenopathies
 Bone pains
- Due to metastasis in the bone marrow which would also cause
Bone marrow failure
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 Subcutaneous nodules in INSS Stage 4S
- Presents with skin nodules, curable and has a good prognosis
even though it’s in Stage 4
Diagnostic Criteria:
 Unequivocal pathologic diagnosis by light microscopy showing a
ROSETTE formation with or without immunohistology, electron
microscopy, or increased urine cathecholamines or metabolites;
or
 Bone marrow aspirate contains unequivocal tumor cells, and
increased urine cathecholamines or metabolites
 Increased Urine Cathecholamine metabolites:
- Homovanillic acid (HVA) and Vanillylmandelic acid (VMA)
INTERNATIONAL NEUROBLASTOMA STAGING SYSTEM
1
Localized tumor with complete gross excision, with or without
microscopic residual disease; representative ipsilateral lymph
nodes negative for tumor microscopically (nodes attached to and
removed with the primary tumor may be positive)
Tumors confined to the organ of origin
2A
Tumors extend beyond the structure of origin but not across the
midline (without ipsilateral LN involvement)
2B
Tumors extend beyond the structure of origin but not across the
midline (with ipsilateral LN involvement)
3
Tumors extend beyond the midline, with or without bilateral LN
involvement
4
Any primary tumor with dissemination to distant lymph nodes;
bone, bone marrow, liver, skin, and other organs (except as
defined for stage 4S)
4S
Localized primary tumor (as defined for stage 1, 2A, or 2B), with
dissemination limited to skin, liver, and bone marrow (limited to
infants <1 yr of age)
CURABLE
Neuroblastoma Risk Groups and Prognosis (Please check the last portion of
the trans for the Table)

Staging

Age

MYCN status
- Most useful parameter for the basis of prognosis of the patient
- >10 copies of MYCN = POORER prognosis

Shimada Histology
- 2nd most useful parameter after MYCN status

DNA Ploidy
- Also a useful parameter.
Management:
 Low Risk
- Surgery for stages I and II
- Observation for Stage 4S
•
Intermediate
- Surgery
- Chemotherapy
- Radiation
•
High-risk
- Chemotherapy
- Bone Marrow Transplantation
Diagnostic Evaluation:
 CBC
 serum Ca2+
 Urinalysis
 Liver function test
 Renal function test
 Abdominal ultrasound
 CT scan with contrast
3RD NATIONAL WILMS TUMOR STUDY STAGING SYSTEM
I
Tumor is limited to kidney and is completely resected. Capsular
surface intact; no tumor rupture; no residual tumor apparent
beyond margins of excision
II
Tumor extends beyond kidney but is completely resected. Regional
extension of tumor; vessel infiltration; tumor biopsied or local
spillage of tumor confined to the flank. No residual tumor apparent
at or beyond margins of excision
III Gross or microscopic residual tumor remains postoperatively
IV Deposits beyond stage III (e.g., lung, liver, bone, brain) METASTATIC
V
Bilateral renal involvement at diagnosis
Poor Prognostic Factors:
 Unfavorable histology of anaplastic nuclear changes
- Similar to the Clear cell carcinoma of the kidney
 Positive lymph node involvement
Management:
 Surgery
 Chemotherapy
- Pre-operative: with tumor extension into the IVC, unresectable
tumors, bilateral renal tumors
 Radiotherapy
- Pre-operative: if unresponsive to pre-op chemotherapy
- Post-operative: given to all Stage III and above who did not
receive pre-op radiotherapy
NEPHROBLASTOMA VS NEUROBLASTOMA
Wilm’s Tumor
 Intrarenal and does not cross the midline
 Does not calcify
Neuroblastoma
 Arise in the celiac axis (adrenal gland or paravertebral sympathetic
ganglia) or extend across the midline because of lymph node
involvement
 Mass often contains calcification and hemorrhage
WILM’S TUMOR/NEPHROBLASTOMA
 Most common primary malignant renal tumor of childhood
 Most are solitary lesions but can also be bilateral
 Can be multifocal:
- 7% of cases involve both kidneys
- 12% of cases have multiple lesions within a single kidney
 More than 85% of cases can be cured by current therapies
Congenital Anomalies Associated With Wilms Tumor:
(Per 1,000 cases)
 WAGR syndrome
 Denys-Drash syndrome
 Beckwith-Wiedemann syndrome
 Hypospadias
 Sporadic hemihyperthrophy
 Cyptorchidism
Clinical Presentation:
 May present the same way as Neuroblastoma but…
- Wilms Tumor rarely crosses the midline while Neuroblastoma has
the tendency to do so.
 Large flank mass that does not move with respiration
 Abdominal pain
 Gross hematuria
 Fever
 Subcutaneous nodules at stage IV
 Hypertension: 25% of cases, due to renal ischemia
 Anemia: bleeding into the renal parenchyma or pelvis
7.5
4.0
10.7
20.0
25.1
46.6
Genetics:
 Wilm’s Tumor appears to result from the loss of function of certain
suppressor genes as opposed to the activation of oncogenes
 WT1 (11p13): Wilms Tumor suppressor gene
 WT2 (11p15): Wilms Tumor activation gene
 FWT1 (17q) and FWT2 (19q): familial locus
RHABDOMYOSARCOMA
 Most common pediatric soft tissue sarcoma
 Accounts for ~3.5% of childhood cancers
 May occur at virtually any anatomic site but usually are found in the
head and neck (40%), GUT (20%), extremities (20%), trunk (10%) and
retroperitoneum
 Incidence at each anatomic site is related to both patient age and
tumor type
 Arises from same embryonic mesenchyme as striated skeletal ms
 Histologic subtypes:
- Embryonal type 60%
 Intermediate prognosis
- Botyroid type 6%
 Variant of the embryonal form
 Tumor cells and an edematous stroma project into a body
cavity like a bunch of grapes
 Found most often in the vagina, uterus, bladder, nasopharynx,
and middle ear
- Alveolar type 15%
 Tumor cells tend to grow in cores that often have cleft-like
spaces resembling alveoli
 Alveolar tumors occur most often in the trunk and extremities
 Has the poorest prognosis
- Pleiomorphic type <1%
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 The “adult form”
 Rare in childhood and accounts for only 1% of cases
- Undifferentiated 20%
Clinical Manifestation
• Mass that may or may not be painful
• Metastatic sites: lungs and bones
BONE SARCOMA: EWINGS VS OSTEOSARCOMA
Differentiation between Ewing’s and Osteosarcoma (SITE)
 EWING’S – Diaphyses of long bones, flat bones; sites of primary
tumors arising in bone are distributed evenly between the extremities
and the central axis (pelvis, spine, and chest wall)
 OSTEOSARCOMA - Metaphysis of long bones
And RADIOGRAPHIC FINDINGS
 EWING’s: X-ray  onion-skinning
 OSTEOSARCOMA: X-ray  sunburst pattern
Other Features:
Feature
Age
Cell
Presentation
Differential
Diagnosis
Metastasis
Treatment
Outcome
Osteosarcoma
2nd Decade
Spindle-cell producing
osteoid
Local pain and swelling,
often history of injury
Ewing’s sarcoma,
osteomyelitis
Lungs, Bones
Chemotherapy (TOC),
ablative surgery of primary
tumor
w/o mets: 70% cured; w/
mets at diagnosis
< 20% survival
Ewing’s Sarcoma
2nd Decade
Undifferentiated small
round cell
Local pain and swelling,
fever
Osteomyelitis, eosinophilic
granuloma, lymphoma,
NBT, RMS
Lungs, Bones
Radiotherapy and/or
surgery of primary tumor
w/o mets: 60% cured; w/
mets at diagnosis: 20-30%
survival
ROUND BLUE CELL TUMOR
 Seen in biopsies of:
- Ewing’s Sarcoma (MIC2; CD99)
- Lymphoma (CD45)
- Neuroblastoma (NSE)
- Rhabdomyosarcoma (Desmin)
Use Immunohistohem to Identify the specific type
GERM CELL TUMORS
Nelson’s part (reading assignment)
 Rare; 12 cases per million person < 20 years
 Most malignant tumors of the gonads in children
 Varies according to age and sex
 Females: Sacroccocygeal tumors in infants
 Males: Testicular GCT before age 4 and after puberty
o
Often in whites than in blacks
o
Increased in first degree relatives
o
Highest among monozygotic twins
 Ovarian GCT in blacks
 Klinefelter increased risk of mediastinal GCT
 Downs, undescended testes, infertility, testicular atrophy and
inguinal hernia = increased risk of testicular cancer
Pathogenesis
GCT
 Arise from primordial germ cells
 Contain benign and malignant elements in different areas of the
tumor,
 Extensive sectioning is essential to confirm the correct diagnosis
 Histologically distinct subtypes of GCTs: teratoma (mature and
immature), endodermal sinus tumor, and embryonal carcinoma
Non GCT
 Arise from coelemic epithelium
 Non-GCTs of the ovary include epithelial (serous and mucinous)
and sex cord/stromal tumors; non-GCTs of the testicle include sex
cord/stromal tumors (e.g., Leydig cell, Sertoli cell).
Testicular and Sacrococcygeal
 During early childhood
 Deletion of chromosome arms 1p and 6q and gains at 1q, and lack
the isochromosome 12p that is highly characteristic of malignant
GCTs of adults
Testicular GCT
 May demonstrate loss of imprinting.
Clinical Manifestations
 Depends on location.
o
Ovarian tumors often are quite large by the time they
are diagnosed.

Extragonadal GCTs occur in the midline,
including the suprasellar region, pineal
region, neck, mediastinum, and
retroperitoneal and sacrococcygeal areas.
 Symptoms relate to mass effect, but the intracranial GCTs often
present with anterior and posterior pituitary deficits
Laboratory Results
** serum and csf should be assayed for these markers with patients with
intracranial lesions**
 Elevated alpha-fetoprotein
o
Elevated in endodermal Sinus tumor
o
Minimally elevated in teratomas
 Beta human chorionic gonadotropin
o
Elevated in choriocarcinoma and germinomas
 Lactate dehydrogenase
o
Non specific but useful marker
o
Provide important confirmation of the diagnosis
o
provide a means to monitor the patient for tumor
response and recurrence
Diagnosis
 PE
 Imaging Studies (plain radiograph of the chest and
ultrasonography of the abdomen)
 CT or MRI can further delineate the primary tumor.
 If germ cell malignancy is strongly suggested, preoperative
staging with CT of the chest and bone scan is appropriate.
 Primary surgical resection is indicated for tumors deemed
resectable.
**Intracranial lesions established with imaging and AFP or β-hCG
determinations **
Gonadoblastomas
 Occur in patients with gonadal dysgenesis and all or parts of a Y
chromosome.
 Gonadal dysgenesis
o
Characterized by failure to fully masculinize the
external genitalia.
o
Ultrasonography or CT
o
Surgical resection of the tumor
o
Prophylactic resection of dysgenetic gonads
o
Gonadoblastomas may produce abnormal amounts of
estrogen.
Teratomas
 Occur in many locations, presenting as masses.
 Not associated with elevated markers unless malignancy is
present.
 Sacrococcygeal region is the most common site for teratomas.
 Sacrococcygeal teratomas occur most commonly in infants and
may be diagnosed in utero or at birth, with most found in girls.
 Rate of malignancy in this location varies,
o
Ranging from <10% in children <2 mo of age to >50% in
children >4 mo of age.
Germinomas
 Occur intracranially, in the mediastinum, and in the gonads.
 Ovary = dysgerminomas
 Testis = seminomas.
 Tumor marker negative despite being malignant.
 Endodermal sinus or yolk sac tumor and choriocarcinoma appear
highly malignant by histologic criteria.
o
Both occur at gonadal and extragonadal sites.
 Embryonal carcinoma most often occurs in the testes.
Non-germ cell gonadal tumors
 Very uncommon in pediatrics and occur predominantly in the
ovary.
o
Sertoli-Leydig cell tumors, Granulosa cell tumors may occur
in children.
o
Carcinomas account for about ⅓ of ovarian tumors in
females <20 yr of age;

Most of these occur in older teens and are of the serous
or mucinous subtype.
o
Sertoli-Leydig cell tumors and granulosa cell tumors produce
hormones that can cause virilization, feminization, or
precocious puberty, depending on pubertal stage and the
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o

balance between Sertoli (estrogen production) and Leydig
cells (androgen production).
Diagnostic evaluation

Hormone measurements, which reflect gonadotropinindependent sex steroid production.

Surgery usually is curative.

TREATMENT
 Complete surgical excision
 Except for patients with intracranial tumors
o
Primary therapy consists of radiation therapy and
chemotherapy.
 For testicular tumors, an inguinal approach is indicated.
 When complete excision cannot be accomplished, preoperative
chemotherapy is indicated, with second-look surgery.
 For teratomas, both mature and immature, and completely
resected malignant tumors, surgery alone is the treatment.
Cisplatin-based chemotherapy regimens usually are curative in
GCTs that cannot be completely resected, even if metastases are
present.
Except for GCTs of the central nervous system, radiation therapy is
limited to those tumors that are not amenable to complete
excision and are refractory to chemotherapy.
PROGNOSIS
 The overall cure rate for children with GCTs is >80%.
 Age is the most predictive factor of survival for extragonadal
GCTs.
 Children >12 yr of age have a 4-fold higher risk of death, and a 6fold higher risk if the tumor is thoracic.
 Histology has little effect on prognosis.
 Nonresected extragonadal GCTs have a slightly worse prognosis.
Neuroblastoma Risk Groups and Prognosis
Risk Group
Survival
INSS Stage
Low
90-100%
Average
High
75-98%
20-60%
Age
MYCN Status
Shimada Histology
DNA Ploidy
1
All
Any
Any
Any
2
<1yr
Any
Any
Any
2
>1yr
Any
Favorable
4S
<1yr
<10 copies
Favorable
3
>1yr
<10 copies
Favorable
3 and 4
<1yr
<10 copies
Any
4S
<1yr
<10 copies
Unfavorable
Any
4S
<1yr
<10 copies
Any
Diploid
2
>1yr
Any
Unfavorable
3
All
>10 copies
Any
4
<1yr
>10 copies
Any
4
<1yr
Any
Any
Shoutouts:
2012, Last trans ko na. Haha, salamat sa oncoboys na pumayag na ako ang mag audio ng
oncotrans. Kina oncovince, oncobjorn at oncorob. Sana hindi naactivate oncogenes nyo
kakahintay sa oncoaudio. Oncongratulations tapos na!
Hyperdiploid
Any
Any
Sa mga boss ko sa trans ng physio (nakalimutan ko na sori), micro (boss chen), para
(boss ewi) at pedia (boss chen).
Hindi ko nga pala nabati ung mga tumulong sa trans ng 5 th long:
Rika – suking transcriber ng pedia
Kaye – recruited transcriber
Unica – nakaw na transcriber from surg transcom
Fao – nanakaw din from surg transcom
Armin – utol ko ‘to. First time magtrans kaya virgin transcriber daw cya sabi nya, haha.
Pag may nakalimutan ako batiin ko na lang pag JI na!
Wohoo.. Last TRANS.. Dahil epic trans to, it requires an epic shout out.. :D Would like to
thank the 1st year, 2nd year and 3rd year edition trans com.. JOB well done.. Thank you sa
lahat ng tumangkilik ng since 1st year.. :D Sa mga parati kong nakakasama homie, dc,
anna.. :D kay mafe (ASAP ah) at achie (hello kay rico).. kay Christine (new strbux buddy)..
:D Chad (shotgun seat) Jubu (banchetto uli).. Basha (kiss the girl.rrrrrr), Would like to say
hi to may ICS group both past and present.. pepet, alex, nadinne, aienne, ewi, mike,
hamid, mel, ren, abi, ms angquino, Carmen, ria.. :D at pa minsan minsan na si eds na
paasa!!! Ana.. binabati na kita.. :D Bacal, salamat sa chocolate. Ej.. hi hi.. kay
alpha!!(want to ride for a spin?) tel(donut ko), mon (starbucks?? )sa beach committe..
(berry aryane rob alex b). :D sana lahat makapunta sa beach.. wohoo.. kaunti nalang..
kay madam, doys, clar, andrea (noh!!) at rucelle  sa mga pretty ladies at guys of prom
night 2..  at boys of joeys..hahaha hi Bianca (level up), abogs( mas pretty barista!),
kaye, bru, farie, CYSt (princess?), psssst, jet, cocai, cathy, jia, ethel, em, pauline, celina,
bunny lian, Carla, tiff, rvin, cecille, erys at ms banta..:D Bi, mia, Carla, marion, lynette,
mav, rose o chuchi?, virra, fx daph abby at sa lahat ng sec b. :D OMAR at Coneil sa
starbucks guys, kay Tristan, at sa lahat lahat na 2012.. ang haba pala mag
enumerate.haha
Group mates ko: abie b, hen, Christine, gretch, kaye, mau, mafe, alex, nico, jumong,
jisoo at syempre ang favorite kong groupmates: BETH and TENG!
Hello kay BING, CKMB <3 !!!!!!
2012, last two weeks of our 3rd year life.. LET’S MAKE IT LEGENDARY!!!
Kay rica de borja na nagpapabati. Binabati kita. Bati na tayo kasi binabati mo naman ako
sa trans mo, haha.
-Vince
– Quillerboy –
Hi guys!!! :D Wuhu!! This is my FIRST and LAST trans in med school! :D next year kaya sa
mga review classes natin meron ulit?!?! Hehe..
Anyway.. I would like to thank Ms. Chen BASTE!!! For forcing us (ONCOBOYS) to make
this trans!! haha thanks chen  and thanks ulit sa SNOW/WATER from Chicago! 
Thank you to my fellow transcribers Vincent, Robin and Quill 
Hi kay Edz (fave sis), Maricar (fave fil-am), Gretz (kahit anong mangyayari papansinin
parin kita haha), Ana(wassup older sister? Haha kelan na ulit tayo mag mmovie?), EJ
(sama ka na sa beach!!), Val (hi lang haha), Bau ( baguio na ulit!), Faye( fave neighbor!
Thanks sa gift!), and Ralph (fave neighbor din!! Hahaha)
Hello sa WOLFPACK! Pat, Pepin and JM, Sama narin si Gelo!! Haha sup bros! MU
LAMBDA!!! :D
Pao!!! Game na!!! gawa na tayo ng sariling BBZ sa unit niyo at mag-sasaya tayo sa
mezza!! Ivan!!! Hahaha dapat kasama ka naming ni pao! Hindi pwedeng hindi 
Hi sa mga una kong ksama sa “Wed is the NEW FRIDAY group” Chad, Carlo and
Rocky/Andrew!
Hi din kay Jen (thanks sa Psalm 54:4!!!!), Jei (thanks din sa Matt 11:28-30 and sa gift!),
Berry, Alex, Abi, Joy (thank you sa pin!!! Ginagamit ko siya ha!), Ewi (the “hassle”
twinny), Farie (the new “evil” twinny! Haha peace), Paul (ditch! haha), Nico BuenaV,
Mau, Nice, Ria, Carmen(thanks for the gift), Anna, Christine, Hen, Abogs (OH! kaw na
ang mag hheatstroke sa SEC A!!! haha), Kay (thanks for the Goldilocks polvoron!!) Mafe,
Rika, Teng! (MY SOURCE OF WISDOM/TRANS), Tel, and hi narin sa lahat!! Sorry kung
may hindi ako nasama sa shout out ko.. malamang masasama din naman kayo sa shout
outs nina Rob, Vincent and Quill.. anyway yun lang!! GO 2012!!!! Tapos na ang lecture
days... Ma-mmiss ko kayong lahat 
-Bjorn
Yahoo! Akin na yung natitirang space! Ang bait mo naman boss! Wahahaha!! :p
ONCOBOYS, job well done sa last pedia trans of our med lives! Mas matagal pa tayo
nagisip ng ilalagay na shoutouts kesa dun sa mismong paggawa ng trans! Hahaha! Boss
Chen, eto na yung EPIC TRANS namin as promised! :D
Sa ICS1 na nag-semi adopt sakin – lexie, giggles, ewi (adik ka sa lipstick), mike, ren, mel,
kxi, abi (see you later dear!), jorge, boss vince (alagaan mo si bing ha XD), carmen (told
ya i’d win! haha!), ria (happy times dapat, hindi emo times :p)..
Sa ICS2 na hindi tinatablan ng terror preceptors – bjorn (yung regalo natin sa isa’t isa!
haha), edz (buti naman at pinagbigyan mo yung bday ko :p), maricar (when’s your bf
coming here??), gretz (2 straight weeks magiging active ang crammer’s club, excited ka
na ba?), banana (anak, iba na lang kagatin mo pls!), ej (bakit ayaw mo sumama samin sa
mall??), val (excited ka na magbeach noh? Haha!), boss chen-chen (nagsisisi ka bang
kami gumawa ng trans na to? lol), bau (ano, road trip ulet tayo?), fayery (hindi na kita
mahagilap ah, kwentuhan naman tayo!), ralph (direk, san ang susunod na shooting?)
Hello to everybody else!! Alcohol Committee – berry, alex, aryane, mau-mau – (kahit
saan na, basta may alak!)... Team Baguio – alpha buenaV (bawal ka mag-absent sa
beach ha!), paul, mae, mother, ralph, ram, abogs (ano? heatstroke?), darlow, mafe,
rika, and ziaaaa – Guesstures ulet sa beach?... Mu Lambda Boys – pat, jm, pepin (stop
it!), at geloboy (peacock 010!) – handa na ba kayo maghasik ng lagim sa ji?...
mariaaaaaa (last 2 weeks of sleepover studying! )... alvin (yung promise mo samin ni
jm di namin makakalimutan!)... jei (bawal magtampo! thanks ulet! :D)... chad (good job
santino! XD)... anna (good day madame :p)... hen (buti naman at sasama ka sa outing
:p)... at sa inyong lahat na di ko na mababanggit dahil di na kasya, hello hello hello!!! :D
Remember: The future belongs to those who believe in the beauty of their dreams...
We can do this guys!! We’re 2012, and we’re AWESOME!!! 
-Rawbean
Page 10 of 10
TRANSCRIBED BY: Vince, Bjorn, Rob & Quill (OncoBOYS)
COPYREAD BY:
P EDIATRICS: Oncology 2012