Pediatric Tumors Kuliah S1 SEPTEMBER 2010

9/26/2014 8:42 PM bambangsdmt@gmail.
com 1
Pediatric Solid Tumors

Bambang Sudarmanto
Hematology-oncology working group
Kariadi Hospital Semarang
Indonesia
9/26/2014 8:42 PM bambangsdmt@gmail.com 2
PEDIATRIC SOLID TUMORS
Bambang Sudarmanto
Hematology-oncology working group
Kariadi Hospital Semarang
Indonesia
Pediatric Tumors
Kariadi Hospital is referall hospital Central Java
and part of Borneo
Class of patients: Jamkesmas (poor people),
Askes (health insurance), private
Many are treated in Private Hospitals
many hospitals do not treat children with
cancer

Pediatric Solid Tumors (<14)
9,000 new cases, 1500 deaths of pediatric
cancers annually in the U.S.
Cancer- 2nd leading cause of death in children
(1
st
infections)
1/3 deaths from leukemia
CNS tumors most frequent SOLID tumors in
pediatric population
Indonesia data not viable (Semarang?)
Pediatric solid tumors
Childhood cancer
requires multidisciplinary treatment groups
emotional needs of patient/family
nutritional needs
coordinated care- medical, surgical,
oncology, nursing, social services,
therapists, educators
Distribution of Childhood Cancer
CNS
18%
Liver
1%
Other
8%
Leukemia
33%
Retina
3%
Germ Cell
3%
Bone
5%
Wilm's
Tumor
6%
Hodgkin's
5%
NHL
3%
NBL
8%
Soft Tissue
Sarcoma
7%
Thyroglossal
Duct Cyst
Infectious/
Inflammatory
Neoplasms
Pediatric Neck Mass
Congenital Acquired
Branchial
cleft cyst
Cystic
hygroma
Dermoid
cyst
Congenital Masses
Thyroglossal duct
cysts
Branchial cleft cysts
Lymphatic
malformations
Hemangiomas
Teratomas
Dermoid cysts

Laryngoceles
Thymic cysts
Vascular
malformations
SCM tumors of
infancy
Plunging ranulas
Acquired Masses
Infectious
Bacterial
Viral
Fungal
Sialadenitis
Inflammatory
Kawasaki
Sinus Histiocytosis
Drug-induced
lymphadenopathy
Sarcoidosis

Abdominal masses
Trends
Abdominal masses are most common in children
under the age of 5 years
Most abdominal masses in neonates are
retroperitoneal, of kidney origin and are not
malignant
The older the child the more likely the mass
represents a malignant process
Abdominal masses
History
Symptoms
abdominal discomfort, increased abdominal
size or assymptomatic
Presence of systemic symptoms
bone pain, limping, malaise, fever
Other symptoms
hematuria

Abdominal masses
Physical findings
Presence of abdominal mass
upper abdomen or lower abdomen
Other associated physical findings
other masses: orbital
bruises
hypertension
pain

Work up two components
Staging
X-ray of primary site
CT chest, abdomen, &
pelvis
CXR (baseline)
bone scan
Bone marrow
Evaluate for complications of the
tumor
CBC with diff
TPN panel
LDH, uric acid tumor
lysis, rapid cell growth
creatinine renal function
Transaminases hepatic
involvement
Specialty tests
Tumor markers
HCG, AFP
HVA/VMA .

Possible Diagnoses of Abdominal Masses in
Infancy and Childhood
Atlas of Pediatric Physical Diagnosis, Fourth Edition
Abdominal Masses in Older Children
Renal 55%
Wilms (& other) 25%
Hydronephrosis 20%
Cystic disease 5%
Non Renal
Retroperitoneal 23%
Neuroblastoma 21%
Teratoma 1%
Other 1%

Gastrointestinal 12%
Appendiceal Abscess
Lymphoma
Hepatobiliary 6%
Tumors
Hepatoblastoma
HCC
Genital 4%
Ovarian Cysts and
Teratoma
Neonatal Abdominal Masses
Renal 55%
Hydronephrosis 35%
Cystic disease 10%
Multicystic dysplastic
Polycystic dysplastic
Solid Tumors 10%
Mesonephric nephroma
nephroblastomatosis
Pelvic / Genital 15%
Teratoma
Ovarian Cysts
Hydrometrocolpos
Obstructed bladder
non-Renal Retroperitoneal 10%
Adrenal
Hemorrhage
neuroblastoma
Gastrointestinal 15%
Duplication
Mesenteric omental cyst
Pseudocyst from
complicated obstruction
Meconium ileus
Hepatobiliary 5%
Hepatic tumors
Hemangioendothelioma
Cystic mesenchymal
hamartoma
Hepatoblastoma
Neuroblastoma
Choledochal cyst
Examination of the Pediatric Abdomen
History time the mass has been present, rapidity of
growth, symptoms
Undress patient: evaluate for genetic or inherited
predisposition as well as the belly
Palpate from the pelvis toward the thorax
Describe location
Size
Consistency
Ascites
Venous congestion of surface

Golden and Feusner, 2002, Pediatr Clin N Am, 49:1369-1392

Abdominal Mass
Differential diagnosis
depends on location
Upper abdominal
mass
Neuroblastoma
Wilms tumor
Hepatoblastoma
Rhabdomyosarcoma
Germ cell tumor
Lymphoma

Abdominal Mass
Differential diagnosis (cont)
Lower abdominal/pelvic
mass
Neuroblastoma
Rhabdomyosarcoma
Germ cell tumor
Lymphoma
Ewings sarcoma

Abdominal Masses
Laboratory evaluation
Bone marrow aspirate
neuroblastoma, lymphoma,
rhabdomyosarcoma or Ewings
sarcoma
CSF tap
if lymphoma is a consideration
Abdominal masses
Radiologic work-up
Abdominal/pelvic ultrasound
useful screening test: helps define location and
quality (solid or cystic)
not useful to assess for retroperitoneal adenopathy
Computed tomography
location of mass
presence of calcification
obstructive signs
Wilms Tumor
Accounts for 6% childhood malignancies
Median age at diagnosis 3 years
Metastasizes to lung and lymph nodes
70% patients present with localized disease

Wilms Tumor: Signs & Symptoms
Most commonly
presents as painless
abdominal mass
Hypertension (20-
30%)
Pain (20-30%)
Hematuria (25%)

Wilms Tumor
Diagnosis:
Ultrasound
CT
Lymph node and lung mets
Right sided tumors- liver mets
Mets to bone and brain possible with some
histologies

Wilms Tumor: Staging System
Stage Definition
I Tumor limited to kidney, completely excised

II Tumor extends beyond the kidney, completely
resected; no residual tumor beyond resection margins
III Residual non-hematogenous tumor confined to
abdomen
IV Hematogenous metastases
V Bilateral renal involvement
Bilateral Wilms Tumor
Survival by Stage and Histology
Histology/stage # pts 2 yr-s
*
4 yr-s
*
FH/I 546 98 97
II 281 96 94
III 290 91 88
IV 126 88 82
UH/I 20 89 89
UH/II-IV 40 56 54
*
survival
Wilms tumor
Treatment:
Remove kidney- nephrectomy
Lymph nodes biopsied
Can spread also through blood
Tumor spill is possible- abdominal cavity is at risk
Chemo and RT- sometimes preop to reduce
tumor spill
RT late stages, residual dx, LN mets,
bilateral dx, lung mets

Wilms Tumor

Chemo
Actinomycin-D
Added vincristine, Adriamycin- 80-100% cure rates
Mets = 70% cure rate

Wilms Tumor: Prognosis & Future Directions
Prognostic factors: stage and histology
Future directions
Minimize therapy for favorable histology
patients
Identify biologic factors predictive of outcome
Intensify therapy for patients with unfavorable
histology


Pediatric Brain Tumors
(CNS Tumor)
Brain tumors: pediatric vs. adult
Adults: 70% of tumors are supratentorial
meningioma
pituitary adenoma
High grade astrocytoma
Anaplastic astrocytoma (grade III)
Glioblastoma multiforme (grade IV astrocytoma)

Pediatric: 70% in posterior fossa
pilocytic astrocytoma (cerebellar astrocytoma)
medulloblastoma
Second most common cancer in children
Most common solid tumor
Leading cause of cancer death in children
Result in more morbidity than any other
malignancy in childhood

CNS TUMORS
Most common solid tumors in children
2
nd
most frequent (16.6% of all childhood
malignancies)
Incidence has increased over the past 2
decades
Leading cause of cancer death in children
Result in more morbidity than any other
malignancy in childhood
Metastatic brain cases are rare

CNS TUMORS
Signs & Symptoms
(related to the location, histologic grade
of tumor & age of child)
General
-Headache
-Seizures
-Mental status changes
-Increased intracranial Pressure (ICP)

CNS TUMORS

Signs & Symptoms-Posterior Fossa
-Cerebellum: -nausea, vomiting, headache,
papilledema, clumsy walk,
double vision, dizzyness

-Brainstem: -vomiting, cranial nerve palsies,
headache, head tilt, personality
changes, hearing loss

CNS TUMORS
S&S-Cerebral Hemisphere
Frontal lobe-one-sided paralysis, memory
loss, mental changes, urinary changes
Occipital lobe-visual changes, seizures
Parietal lobe-Language disturbances,
seizures, loss of reading, math
Temporal lobe-seizures, unable to recognize
sounds, visual impairments

CNS Tumors Astrocytomas

Tumors originating from nonneural
supporting cells of the brain; glial cells
Low-grade vs. High-grade
Low-grade
Long history of mild symptoms
Symptoms include: worsening headache, degenerating
coordination, visual impairment, poor school
performance
eventually may progress to seizures
Can be watched until child is 3-5 and brain is more
mature
Low-grade Astrocytoma
Neurosurgery is primary treatment
If no residual disease there is a 90-
100% cure rate
RT reserved for positive margins,
recurrent disease, inaccessible tumors
(50-55 Gy @ 1.8 Gy fxs)
Modern Chemo is being investigated

High Grade Astrocytomas

High Grade
fast growing
spread distantly and through CNS
Order of increasing malignancy:
anaplastic astrocytoma
glioblastoma multiforme
malignant primitive neuroectodermal tumor - PNET
Symptoms are aggressive
steroids used to reduce edema

Staging not routinely used
Neurosurgery first important treatment
provides diagnosis
removes gross disease, usually leaves residual
disease
relieves pressure and decompresses other cranial
structures
provides histology
Chemo/RT standard after surgery
Chemo can delay use of RT until brain matures

One treatment regimen
RT to the Whole Brain
30 Gy, boost to 60 Gy
CSI- treat whole CNS
includes the spinal canal (from behind the eye to
midsacrum)
due to cerebrospinal fluid seeding
Prognosis is poor
5 yr survival 20-35%
Optic Gliomas

optic tract and hypothalamic gliomas
extremely low-grade (malignant?benign)
can affects vision and hormonal functions
Chemo or RT if symptomatic

Benign CNS Tumors

Pituitary Adenomas
excessive hormone production
visual disturbances from pres. on optic chiasm
Diabetes insipidus (DI)
Surgery primary treatment
Bromocriptine (drug-counteracts hormone
production)
RT 45Gy, if other methods fail

9/26/2014 8:42 PM
bambangsdmt@gmail.com
46
Benign CNS Tumors

Craniopharyngiomas
Arise from embryonic remnants of pharyngeal pouch
tissues
Can disrupt hypothalamic pituitary axis , impair
vision, induce seizures
Surgery and radiation used to treat symptoms
Meningiomas and Acoustic Neuromas (Ben.)
treated if symptomatic
Arteriovenous Malformations
Radiosurgery typically used if surgery is not an
option- control bleeding 80% cases
15-20 Gy given in a single fx
Medulloblastomas
25% of all childhood brain tumors
Occurs in the posterior fossa
Arises in the midline of the cerebellum and spreads to the in the
4th ventricle and brain stem
High propensity to spread through CSF
2-12 yr old
peaks at 5 yr old
Rare in adults
arises from primitive neuroepithelial cells
histologically cells appear as small, round, blue cells
forming pseudorosettes. Purple friable tumor
Medulloblastomas

invasion of the fourth ventricle causes sx
CSF does not flow causing hydrocephalus
headaches early- morning vomit get progressively
worse
Ataxia
cranial nerve abnormalities from invasion of the
brain stem
Staging correlates with survival
CT/MRI, myelography of entire CNS necessary

Medulloblastomas
Can develop mets in bone
Neurosurgery is first treatment
remove gross disease
ventricular shunts are discouraged because of possible
seeding into peritoneal cavity
CSI- Craniospinal Irradiation
postop- RT
lateral- opposed brain fields
cover retroorbitally through mid-cervical cord
The divergence of the spinal field determines the collimator
twist

Depending on the length of the spine, two spinal
fields may be necessary
Whole spine is treated- down to S2 or S3
Electrons are used many times to avoid treating
anterior structures
Gaps (photons) between fields are feathered
Some institutions are encouraging a small gap
between lateral brain fields and the upper spinal field
See page 326 Red

CSI -Craniospinal Irradiation
Immobilization important
What position?
Anesthesia may be necessary
RT Doses:
1.5 Gy day to 36 Gy
Boost to posterior fossa area- 54 Gy @ 1.8
day
Chemo investigation
Pediatric Brain tumor
Side effects
nausea- often necessary premedicated
nutrition must be monitored closely
gastrointestinal toxicity
low blood counts
infection
Alopecia
emotional traumas
survival- 60%

More CNS Tumors that can spread into CSF by
seeding
Ependymomas
CSF seeding likely in cases that involve the
infratentorial and anaplastic ependymomas
If seeding is noted or high-risk, CSI

More CNS Tumors that can spread into
CSF by seeding
Germ Cell Tumors- germinomas
Develop from embryological tissue in the midline
from the brain down to the testes or ovaries. May
seed into CSF
Pineoblastomas
CSF seeding also possible
Brain stem gliomas
Involve cranial nerve deficits
Most are unresectable
Affect vision, facial nerves, swallowing- often high-
grade astrocytoma
RT is primary treatment
fields should cover entire brain stem and midbrain
to C1
BID fx (1.0-1.17) to 78 Gy
Poor prognosis- 10%
Late Effects of Treatment
Are worse the younger the age of child at time
of treatment
Post surgical deficits- last for remaining
lifetime
motor-sensory loss
poor coordination
cranial nerve dysfunction

Late Effects of Treatment RT
Intellectual abilities
Whole brain RT to high dose for gliomas and CSF
seeding tumors
decreased intelligence for survivors
Side effect of RT and Chemo
methotrexate and RT- degeneration of white matter
Cisplatin and RT- hearing loss
Pituitary and hypothalamus
doses over 20 Gy can cause decreases in pituitary hormones
thyroid and growth hormones are most likely and can be
reversed with supplemental hormones
CSI- can reduce height of vert bodies = shorter adult
high doses to brain cause permanent hair loss
2nd malignancy
Retinoblastomas
PNET of the retina
Most common intraocular tumor in children
200 U.S. annually (Indonesia: no data)
Most occur 6 mos-4yrs old
Hereditary risk factors- 10% of cases
Can be bilateral- 35% cases
Rarely curative
Retinoblastomas
Discovered by light reflex
White vs. red
Ophthalmologist exam
No biopsy
Avoid possibility of vitreous seeding
CT: detect extraocular extension

Retinoblastomas
CSF disease
Assessed by lumbar puncture
Bone marrow may be biopsed
Staging systems developed
Preferred treatments outlined
Predict success rates
Most common
Reese-Ellsworth

Retinoblastomas
Treatment Techniques
Photocoagulation
Cryosurgery
Small tumors not near optic disc and macula
Enucleation
Unilateral disease
Sacrifices globe

Retinoblastomas
Treatment Techniques:
Surgery
Radiation Implants
RT
Inoperable or bilateral dx
Spare lens and cornea
Treat retina

Retinoblastomas
RT Methods:
Combined Lat/Ant field
Block lens ant field
1.8-3.0 Gy fx (3-5 fx.s a week)
Implants used if dx less extensive
Cobalt 60, Iodine 125
40-60 Gy week
80% cure rate, vision preserved
Retinoblastomas
Treatment Method: if disseminated dx
Chemo
Good response expected
VAC- Vincristine, Adriamycin, cyclophosphamide
OPEC- vincristine, cisplatin, etoposide,
cyclophosphamide

Retinoblastomas
Enucleation
Several prosthetics will be needed as child grows
RT
Facial growth affected
Small orbits
Blind spots
Radiation retinitis, and dry eyes
2nd malignancy
Neuroblastomas
500 cases annually U.S.
2nd most common pediatric solid tumor-
after brain tumors
Age range- newborns-several yrs old
Median age 2 yrs old

Neuroblastomas
Occur mainly in the abdomen
Originate in adrenal gland or paraspinal ganglia
Lethargic, ill appearing child under 2 with
abdominal mass is common
Spinal cord invasion will promote neurological sx
Horners syndrome present with upper
sympathetic ganglia involvement
Flushing, diarrhea

Neuroblastomas
Many children present with mets
Children older than 18 months have 70%
chance of developing mets
CT- chest, abd (US)
Lungs and liver assessed
MRI spine
Bone marrow biopsy
Bone scan
Neuroblastomas
Prognosis
Dependent on age at presentation
< 1 yr old disease may regress if acute sx are
managed
Treatment Techniques
RT and chemo- low cure
Surgery if no mets- high cure rate
Chemo and BMT
RT- palliation
Lymphoma
Lymphomas
3
rd
most common cancer in children. 60% are
NHL; 40% Hodgkins disease
Extranodal disease is common in children with
1/3 rd involving the mediastinum, abdomen or
head and neck
Multi agent chemotherapy is the mainstay of
treatment, surgery and radiotherapy
Anticipation and treatment of complications is
extremely important (lysis tumor syndrome, SVC
syndrome)
Non Hodgkins lymphoma
NHL result from malignant proliferation of
cells of lymphocytic ar histiocytic linage.
Generally restricted to lymphoid tissue
such as lymphnodes and spleen
NHL categorized as low, intermediate and
high grade on the base of their clinical
aggressiveness.
Epidemiology :
peak is between 5-15 years median age 9
years; male preponderance , 3:1
Increase risk include patient with immunologic
defect (AIDS, etc), immunosuppresive therapy
(post transplant)
EBV is almost invariably associated with the
African Burkitts lymphoma
Clinical feature:
are varied depend on the location of the tumor, the
extent of the disease (stage) and histologic subtype
Extranodal involvement :
Mediastinum: may produce SVC syndrome
Abdomen: ileocaecal region, appendix, colon and
retroperitoneal area. Cayse pain, vomiting,
intussuception, ascites, obstructive
Head and neck: enlargement of cervical node, paritis,
tonsilar hyperthropy; jaw swelling
Diagnosis and staging:
History and physical exam
Blood count, BMA and Biopsy
LDH level
Evaluation of liver test (bil, SGOT/SGPT;
alkphospatase)
Chest radiography; USG; CT Scan abdomen
Adequate surgical biopsy
Staging:
Stage I: a single tumor (extranodal) or single
anatomic areawith exclusion of mediastinum
and abdomen
Stage II: stage I + two or more nodal area on
the same side of diaphragna
Satege III: stage II + all extensive node
enlargement
Stage IV: stage III + with initial involvement of
CNS or bone marrow or both

Principal therapy :
Multi agent chemotherapy : CHOP
Anticipation and treatment of complication:
Two complication :
- Arising Space occupying tumor:
intrathoracic complication
pericardial effusion
- Metabolic complication of chemotherapy:
tumor lysis syndrome
Management of relaps
Bone tumors
Benign and malignant tumor
Fracture pathologic
Plain radiography is lytic bone lesion;
cortical destructions soft tissue extension.
Two most common cancers of bone :
osteosarcoma and Ewing sarcoma and the
fascinating group of disorders known as
histiocytosis
Osteosarcoma
Epidemioloy and etiology:
Most frequent adolescent and young adults
Annual 600 new cases in USA
Correlated with radiation exposure
Incidence increase among survival
retinoblastoma (Rb) and p53 tumor supressor
gen.

Osteosarcoma
Pathology:
Clinical history and radiographic appereance
of bone lesion
Correct diagnosis requires of bone biopsy
Biology :
Genetic alteration occur in the tumor
suppresor genes p53 and Rb to play
important role in tumorogenesis

Osteosarcoma
Pathology:
Clinical history and radiographic appereance
of bone lesion
Correct diagnosis requires of bone biopsy
Biology :
Genetic alteration occur in the tumor
suppresor genes p53 and Rb to play
important role in tumorogenesis

Osteosarcoma
Clinical presentation:
Painful hard of the bone
History of trauma
Osteosarcoma can occur in any body but usually
develop in metaphysis of long bone, common site is
distal femur; proximal humerus,
Systemic symptom are fever, night sweats, weight
loss.
Metastatic disease: other bone; pulmonary; soft tissue

Osteosarcoma
Diagnosis and staging:
Plain radiography lytic and/or sclerotic bone
abnormality
A sunburst appearance
Cortical distruction and periosteal reaction
MRI and biopsy

Osteosarcoma
Treatment : local control of tumor and systemic
therapy to eradicated microscopic metastasis
disease at distant sites
Preoperative chemotherapy : reduced tumor bulk;
prognostic implication; making surgical resection
easier
HDX MTX; doxorubicin and cisplatin
Post operative chemotherapy 12 month
Non metastatic disease : 60 -65% to be cured
Metastatic diseases indicated poor prognosis

sarcoma
Ewing sarcoma
Ewing sarcoma is one of a group of
tumors referred to as the Ewing sarcoma
family tumors (ESFT): Ewing sarcoma of
bone; soft tissue Ewing sarcoma and
peripheral primitive neuro ectodermal
tumor (PNET)
Arise from share the same chromossomal
abnormality
Ewing sarcoma
Epidemiology and etiology
Less than 20 years at diagnosis
Annual incidence 2.7 case permillion
The cause of ESFT is unknown, unrelated
with radiation
Pathology and biology:

Precuss

Soft Tissue Sarcomas
Arise from mesenchymal tissue
Can arise anywhere in body
Wide variety of histologies
Most common 60 %
Rhabdomyosarcomas
Undifferentiated

Diagnosis and Staging
Depends on area involved
H&N, genitourinary, extremities and trunk
A large painless mass- extremity
Painful orbit
In genitourinary areas- urinary problems
(male)
Exophytic mass vagina
Mets to lung and bone marrow most common

Staging
Physical exam
US
CT or MRI
BM biopsy/Chest CT (mets)
Stage and histology dictate tx

Staging

Treatment
Surgery
First choice is removal
RT
Improves local control, spare organs
Field covers entire muscular compartment
50.4 Gy 1.8 Gy fx
Shield growth plates
Spare BM in pelvis if possible
Brachy
Chemo- resected/nonresected tumors
Vincristine and actinomycin-D
Unusual Childhood Tumors
Germ Cell Tumors
Can occur anywhere in the midline from CNS to
ovaries and testes
Sacrococcygeal teratomas often seen in newborns
Nonseminomas
Embryonal carcinoma
Choriocarcinoma
Yolk-sac tumors
These often produce AFP, HCG chemical markers
Seminoma- dysgerminoma

Liver tumors
Appear much like Wilms tumor or
neuroblastoma
CT or US will differentiate
Hepatoblastoma- under 2 yrs old
Hepatocellular carcinoma- after 10 yrs old, multifocal
Surgery- primary tx
Chemo- often used
RT- rarely used
Poor survival rates
Histiocytosis X syndromes
Spectrum of disease
Involves Langerhans cells
Miscellaneous Tumors
Nasopharyngeal angiofibromas
Undifferentiated nasopharyngeal
Thyroid tumors- benign and malignant, Iodine 131-
ablation
Keloids or fibromas
Kaposis sarcoma
Pediatric Patients- Special
Considerations
Extra Time Needed
Anesthesia
Psychosocial needs of family- jobs/home
Understanding/compassionate therapist
Use of rewards- stickers/toys
Protocols
Info sent for immediate review
Careful adherence to guidelines important

THANK YOU

Pediatric Tumors Kuliah S1 SEPTEMBER 2010

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9/26/2014 8:42 PM bambangsdmt@gmail.

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