Central nervous system malignancies are the most common malignant solid tumors in childhood, accounting for 20% of cancers. The most common types are medulloblastoma, astrocytoma, ependymoma, and germinoma. Risk factors include genetic syndromes like neurofibromatosis. Symptoms depend on tumor location and type, and can include increased intracranial pressure, neurological deficits, and endocrine abnormalities. Diagnosis involves imaging like MRI and biopsy. Treatment involves surgery, radiation, and chemotherapy. Prognosis depends on tumor type and extent.

1. Central nervous system
malignancies

2. • Commonest malignant solid tumors in
childhood
• 20% of cancers in age < 15 years
• Annually 20 – 26/ 1 million children below
the age of 16 years
• Age –stratified incidence is:
<1year - 27/ 1 million
1 – 4 - 31/ 1 million
5 – 9 - 27/ 1 million
10 – 14 - 20/ 1 million
• Slightly higher frequency in boys 1.25:1
(especially for medulloblastoma and
germinoma)
Epidemiology

3. Etiology and pathogenesis
• Association between primary CNS tumors and following
conditions/ genetic disorders :
1. Neurofibromatosis (NF) type 1 and 2
2. Tuberous sclerosis
3. Von Hippel- Lindau syndrome
4. Gordlin’s, Cowden’s, Turcot’s syndromes
5. Li-Fraumeni syndrome (mutation of suppressor
oncogene p53)
• Deletion of chromosome 17 or 20 (medulloblastoma)
• Exposition of the brain to ionizing radiation i.e. after
cranial radiotherapy in leukemia

4. Pathology
• Supratentorial lesions (30 – 40%):
1. Cerebral hemisphere ( astrocytoma,
ependymoma, glioblastoma, meningioma)
2. Sella or chiasm ( craniopharyngioma,
pituitary adenoma, optic nerve glioma)
• Infratentorial lesions (60 – 70%)
1. Cerebellum (medulloblastoma,
astrocytoma, meningioma)
2. Brain stem ( astrocytoma, ependymoma,
glioblastoma)

5. Classification
• Based on histogenesis and predominance
of cell type
• Degree of malignancy is defined by
grading system e.i. WHO grade based on
cellular morphology, mitotic index,
anaplasia and necrosis:
grades I and II represent benign tumors
grades III and IV - malignant tumors

6. Clinical presentation
• Depends on :
-age
-anatomical site
-tumor type
• -raised intracranial pressure (ICP)
-localizing neurological deficits

7. Signs of increased ICP
• Direct tumor infiltration
• Compression of normal structures
• Secondary to obstruction of the
cerebrospinal fluid (CSF)

8. • Older children:
-inilially behavioural changes and declining school
performance prior to development of the more classical
features of headache, nausea and vomiting ,
headaches start as generalized and intermittent >
increase in both intensity and frequency with time - the
child may awake with headache at night, with the pain
generally being worse in the morning and improving
during the day with an upright posture
-School-age children complain of visual disturbances

9. • Infants and younger children:
plasticity of the developing skull and inability to
communicate symptoms >
-infant may be irritable, with failure to thrive,
associated with anorexia and vomiting
-regression of developmental milestones
-increase head circumference with widened
sutures and a tense anterior fontanelle
„sun-setting” sign

10. Symptoms and signs according to
anatomical site of CNS tumors
• Supratentorial (30-40%)
Cerebral hemisphere- hemiparesis, spasticity, seizures (focal or
generalized)
- para/suprasellar – endocrinopathy (growth failure, diabetes
insipidus, pubertal abnormality)
- hypothalamus – diencephalic syndrome (infants), developmental
and behavioural abnormalities
- optic pathway – visual field acuity, color vision deficits, optic
atrophy, nystagmus, head tilt
- pineal - Parinaud’s syndrome, sleep abnormalities
- thalamus, basal ganglia – pain, sensory loss, memory disturbances
- intraventicular
- meningeal

11. • Infratentorial (60 – 70%)
- posterior fossa – ataxia, nystagmus, dysmetria (presents as
clumsiness or worse handwriting)
- brainstem – multiple cranial nerve palsies, hemiparesis, spasticity,
mood changes
• Spinal (2 – 5%)
- primary intramedullary – pain (local back and root pain), motor and
sensory disturbance
- spinal metastases – scoliosis, sphincter (bowel, bladder)
disturbances, reflex changes

12. Diagnostic evaluation
• Magnetic resonance and computed tomography –
basic imaging techniques for brain tumors
• Positron emission tomography – help to distinguish
tumors or lesions with a volume greater than 1 cm3
• Conventional radiography of the skull: bone structure,
separating off sutures ( due to ICP), calcification within
the brain
• Special methods (for special indications):
- brain scintigraphy
- angiography
-ultrasonography
-myelography

13. Additional diagnosis
• Cerebral fluid analysis ( to determine
spread of the tumor to the spinal fluid)
• Electroencephalography
• Stereotactic biopsy

14. Therapy
• Neurosurgery for maximum tumor removal and low
morbidity depending on the location and extent of the
tumor
-often preoperative relief of intracranial pressure by
ventriculoperitoneal or ventriculoarterial shunt
- preoperative reduction of tumor edema by
corticosteroids
- in patients with seizures - anticonvulsive therapy

15. • Radiotherapy – extension and volume of
irradiation depend on the biology and
histology of the tumor, age of the child and
combination with chemotherapy and
neurosurgery
- irradiation in children < 3 years of life only
in special cases
• Chemotherapy – depends on tumor type,
location and age -efficacy and penetration
depend on vascularization of the tumor

16. MR spectra and MR
images of medulloblastoma

17. 8-year-old girl with juvenile pilocytic
astrocytoma

18. 2-year-old boy with atypical teratoid-
rhabdoid tumor

19. Neuroblastoma

20. • Malignant, embryonal tumor derived from precursor cells
of sympathetic ganglia and adrenal medulla
• Other types of tumors derived from sympathetic nervous
system:
-ganglioneuroblastoma
-ganglioneuroma
-pheochromocytoma
• Possibility to spontaneous regression and differentiation
to benign tumor in infants less 1 year of age
extremely malignant in older children

21. Epidemiology
• 8% of all neoplasms in children
• Most frequent malignant neoplasm in
infants
• Mean age at diagnosis 2 – 5 years

22. Pathology
Two distinct entities:
• Infant:
1. possibility of spontaneous regression
(apoptosis or differentiation into
ganglioneuroblastoma)
2. chemosensitive, chemocurable
• Older
3. chemoresistant malignancies

23. Molecular cytogenetics
• MYCN oncogene amplification.
MYCN is located on chromosome 2p.
Independent prognostic factor:
in stage III EFS for patients with a single copy is curable 80%;
for those with amplification MYCN – 20%
• DNA ploidy: hyperploidy = good prognosis
• Nerve growth factor receptor: ligands for high –affinity tyrosine
kinase receptors TRKA, TRKB, TRKC:
-TRKA expression is associated with MYCN single copy, low stage
and good prognosis
- TRKA (-) + MYCN amplification= very poor survival
• Structural and numerical abnormalities of chromosome 1

24. Clinical manifestation
• Occurence in any area with sympathetic nervous
system
Primary location:
-abdomen 65%
-adrenal medulla or sympathetic ganglia 46%
-posterior mediastinum 15%
-pelvic 4%
-head and neck 3%
-others 8%

25. Common symptoms
• Weight loss
• Fever
• Abdominal disturbances
• Irratability
• Pain of bones and joints
• Child not stand up, not walk
• Pallor
• Lassitude

26. Symptoms associated
with catecholamine production
• Paroxysmal attacks of sweating, flushing,
pallor
• Headache
• Hypertension
• Palpitation

27. Paraneoplastic syndromes
• VIP syndrome: untreatable diarrhea,with low
level of potassium
• Opsoclonus- myoclonus
• Anemia, trombocytopenia, leukopenia
( in bone marrow infiltration or massive
hemorrhage)

28. Local symptoms
• Abdomen:
-intra-abdominal tumor
–paravertebral and presacral -neurological dysfunction
-abdominal distension
• Liver:
-hepatomegaly
• Chest, posterior mediastinum, vertebrae:
-compression of trachea > coughing, dyspnea
-infiltration in vertebral foramina > dumbbell tumor
-compression of nerves >disturbances of gait, muscle
weakness, parasthesia, bladder dysfunction,
constipation

29. • Eyes:
-periorbital edema, swelling, yellow- brown
ecchymoses
-proptosis and exophthalmos, strabismus,
opsoclonus
-papillary edema, bleeding of the retina, atrophy
of the optic nerve
• Neck:
-cervical lymphadenopathy
-supraclavicular tumor
-Horner syndrome: enophthalmos, miosis, ptosis,
Raccon eyes

30. • Skin:
- subcutaneous nodules of blue color > reddish > white
owing to vasoconstriction from release of
catecholamines after palpation
- nodules are mainly observed in neonates or infants
with disseminated NBL
• Bone:
-pain
involvement mainly in the skull and long bones
- in X-rays – lytic defects with irregular margins and
periosteal reaction
• Bone marrow:
-trombocytopenia, anemia

31. Metastases
• Lymphatic and/or hematogenous spread
• Often initially present in children
(40 – 50% children < 1 year and 70%
children > 1 year)
• Metastatic spread mostly in bone marrow,
bone, liver, skin

32. 2-year-old-girl with abdominal neuroblastoma

33. CT image with large abdominal neuroblastoma

34. 123-MIBG
scintscan

35. International Staging System for NBL(INSS)
• 1 - localized tumor with complete excision,lymph nodes negative
• 2a - localized tumor without incomplete gross excision, representative,
ipsilateral nonadherent lymph nodes negative for tumor
microscopically
• 2b – ipsilateral nonadherent lymph nodes positive for tumor. Enlarged
contralateral lymph nodes negative microscopically
• 3 – unresectable unilateral tumor infiltrating across the midline,with or
without regional lymph node involvement or localized unilateral tumor
with contralateral regional lymph node involvement or – midline tumor
with bilateral extension by infiltration or by lymph node involvement
• 4 – any primary tumor with dissemination to distant lymph nodes, bone,
bone marrow, liver, skin or other organs (except as defined for stage
4S
• 4s localized primary tumor (as defined for stages 1, 2a, 2b) with
dissemination limited to skin, liver or bone marrow; limited to
infants aged less than 1 year)

36. Laboratory findings
• Tumor markers:
-catecholamines:
vanillylmandelic acid (VMA), homovanillic acid
(HVA) dopamine in urine/ plasma
adrenaline, noradrenaline
-neuron-specific enolase (glycolitic enzyme of
brain and neuroendocrine tissues) -NSE
• Ferritin
• Lactate dehydrogenease (LDH)
• Bone marrow (aspiration and biopsy)

37. Locoregional involvement
• Computed tomography scan and/or
• Ultrasound and/or
• magnetic resonance imaging →
localize the mass, provide measurements,
give anatomical information about intra- and
extraperitoneal structures, differentiate cystic
from solid tumors, define the extent of a primary
tumor and its relationship with other structures,
detect small calcification

38. Evaluation of metastases
• Bone marrow metastases – bone marrow
aspiration and trephine biopsy
• Skeletal metastases - X-ray, Tc-99
scintigraphy,
• mIBG scintigraphy demonstrates primary,
residual tumor masses,diffuse bone marrow
infiltration, skeletal, lymph node and soft tissue
metastases
• FDG-PET scanning

39. Therapy
Depends on: age, stage, localization and molecular
features at diagnosis
• Surgery
• Chemotherapy
IV stage
• Radiotherapy
• Target radiotherapy (I-131-mIBG)
• Differentiation therapy (retinoids 13-cis and all-trans)
• Immunotherapy: anti-GD2 antibodies
• Auto-BMT

40. Prognosis
• Depends on:
-age (favorable if less than 18 months of age at
diagnosis), -stage and localization (favorable in primary
NBL of thorax, presacral and cervical)
-involvement of lymph nodes (poor prognosis)
• Low-risk group - 90% long-term survival
• Intermediate and high-risk groups:
-response to initial treatment 60-70% of children with
complete or partial remission
-after consolidation therapy (high-dose chemotherapy+
autologous stem cell support) –EFS after 3 years is 40-
60%

41. Hepatic tumors

42. • Malignant:
-hepatoblastoma 43%
-hepatocellular carcinoma 23%
-sarcoma 6%
• Benign:
-vascular (haemangioma,haemangioendothelioma) 13%
-hamartoma 6%
-others 9%

43. Incidence (malignant)
• -1.2 –5% of all neoplasms in childhood
• Boys: girls 1.4 –2 :1
• High incidence in genetically associated syndromes:
-Beckwith-Wiedemann syndrome, familial adematous
polyposis, trisomy 18, glycogen storage disease,
hereditary tyrosinemia, Li-Fraumeni syndrome
• HBL –mostly in infants, rarely after the age of 3 years
• Hepatocellular Ca – in older children, in adolescents,
after hepatitis B

44. Clinical symptoms
• Abdominal mass and/ or abdominal distention
• Anorexia, weight loss
• Lethargy
• Jaundice and ascites
• Abdominal pain
• Pallor
• Precocious puberty (hepatoblastoma), virilization (due
to gonadotrophin production by the tumor)
• Generalized osteoporosis (HBL)- tumor cells secrete
osteoclast-activating factor

45. Laboratory diagnosis
• Serum AFP elevated in 80 - 90% of children with HBL
and in 60-70% with hepatocellular Ca
• B-HCG elevated in both
• Increased bilirubin
• Increased serum aspartate aminotransferase (AST),
alanine transaminase (ALT) because of associated
hepatitis or cirrhosis
• Anemia, thrombocytosis, trombocytopenia (rarely)
• biopsy

46. Radiological diagnosis
• Ultrasound – liver enlarged, displacement of stomach
and colon, elevated diaphragm on the right side
• CT, MRI
• Liver scintigraphy
• metastases: chest X-ray, lung CT
HBL hepatocellular carcinoma

47. Treatment
• Presurgical chemotherapy (makes HBL resectable)
• Complete resection (initially > 50% of liver tumors are
not totally resectable)
• Liver transplantation
Prognosis:
• Depends on stage of the tumor
after complete tumor resection and chemotherapy
65-75 % children with HBL
and 40-60% with hepatocellular Ca survive

48. Germ cell tumors (GCT)

49. • Develop from embryonal germ cells
• Represent ectodermal, endodermal and mesodermal
lineages
• Approximately 3% of childhood malignancies
• Annually 2.4 – 3.8/ 1 million/per year
• 2/3 GCTs in children occur in extragonadal sites
• The commonest GCT - sacrococcygeal teratoma
• Bimodal age distribution:
one peak in children < 3y ears of age (sacrococcygeal
tumors, yolk sac tumors of testis)
- the later- the later GCT of the ovary, testis, and
intracranial sites

50. Histological classification of gonadal and
extragonadal tumors
• Germ cell and germinoma/ dysgerminoma and embryonal yolk sac
tumor (pluripotent cells)
a)extraembryonic structures
- yolk sac or endodermal sinus tumor
- choriocarcinoma
b) embryonal ecto-, meso-, endodermal origin tissues represented
-teratoma
c) embryonal carcinoma
• Gonadal germ cells and stroma tumor (Sertoli and Leydig cells)
• Epithelial cells (ovarian origin) and granulosa cell tumor or mixted
form as well as epithelial cell tumors more common in adults

51. Clinical symptoms
• Testicular GCT :scrotal enlargement,hydrocele
• Ovarian tumors: abdominal pain, acute abdomen,
abdominal mass
• Extragonadal GCT: main sites of involvement:
-sacrococcygeal:
t.1- (47%) predominantly external,
t.2 -both external and intrapelvic
t.3 -external, pelvix and abdominal
t.4 –entitely presacral,
-mediastinal (dyspnea, wheezing, thoracic pain,
superior vena cava syndrome),
-intracranial (visual disturbances, diabetes insipidus,
hypopituitarism, anorexia, precocious puberty)

52. Ovarian and testicular GCT

53. Sacrococcygeal tumor in newborn

54. Diagnostics
Radiological diagnosis:
ultrasound, computed tomography or magnetic
resonance imaging
• Tumor markers:
alpha-fetoprotein (AFP)- globulin produced in the
fetal yolk sac, in embryonal hepatocytes and in
gastrointestinal tract. Increase in malignant GCT,
hepatoblastoma
• Newborns 48,000+/-34,000IU
• Up to 1 month 9,000+/-12,000
• Up to 2 months 320 +/-280
• Up to 4 months 74 +/-56
• Up to 6 months 12+/-10
• Up to 8 months 8+/-5
beta -human chorionic gonadotropin (HCG) –
increase in germinoma/ dysgerminoma,
choriocarcinoma

55. Therapy
• Depend on:
• stage, location, tumor markers level
• Surgery in stage I
• Advanced stages: chemotherapy, surgery, radiotherapy
Survival
95% - sacrococcygeal teratoma
80% -yolk sac tumor

56. Wilms’ tumor
Nephroblastoma

57. • Malignant embryonal tumor of renal tissue consisting of
varying proportion of blastema, stroma and epithelium
• Epidemiology:
6% of all neoplasms in children
80 % of children at diagnosis are less than 5 years old
peak incidence between 2nd and 3rd year of age
- incidence slightly higher in boys

58. Genetics
Chromosomal association:
• Chromosome 11p13 with Wilms tumor suppressor gene WT1
in 10-30% of nephroblastoma
• Chromosome 11p15 with Wilms tumor suppressor gene WT2
• Chromosome 17q with familial FWT-2
Association with congenital anomalies:
-WAGR syndrome: Wilms tumor, aniridia, genital malformation,
mental retardation)
-Denys+Drash syndrome – pseudohermaphroditism,
glomerulopathy, mutation on chromosome 11p
-Beckwith Wiedemann syndrome- hemihypertrophy,
macroglossia, omphalocele, visceromegaly, associated with WT2

59. Clinical manifestation
• Abdominal mass- visible and/or palpable - 70%.
Palpation must be done with care – risk of tumor rupture or
dissemination!
• Fever
• Vomiting, anorexia
• Hematuria (micro or macro) 20-25%
• Hypertension in renin-producing tumors
• Pain 44%
• Special symptoms in association with congenital
anomalies

60. Laboratory diagnosis
• Urine: hematuria
• Chemistry: high serum calcium in children with rhabdoid
nephroblastoma
• Acquired von Willebrand coagulopathy in about 8% of
patients
• Differential diagnosis of NBL: 24-h urine catecholamine
analysis
• Biopsy – only in children with unclear presentation or
diagnosis

61. The child with Wilms tumor

62. Radiological diagnosis
• Ultrasound
• Computed tomography
• Magnetic resonance imaging
=anatomy of tumor extend of any spread within abdomen
Metastases:
• Chest radiographs (posteroanterior and lateral) to exclude
pulmonary metastases
• Angiography may be indicated in bilateral nephroblastoma
• Radioisotope scans , skeletal survey in patients with suspected
skeletal metastates
• CNS MRI in clear-cell sarcoma or rhabdoid kidney sarcoma and in
patients with possible brain metastases

63. Wilms tumor – pulmonary metastatic disease

64. Wilms tumor – intraoperative view

65. Prognostic factors
• Histological appearance „ favourable, unfavourable”
• Histology: rhabdoid tumor
• Diffuse anaplasia
• Viable malignant cells after preoperative chemotherapy
• Infiltration of tumor capsule
• Invasion of tumor cells into vessels
• Nonradical surgical resection of tumor
• Lymph nodes involvement
• Tumor rupture
• Metastatic spread
• Large tumor volume

66. Stage
National Wilms’ Tumor Study Group staging system
I – tumor confined to the kidney and completely resected
II- tumor extend beyond the kidney but is completely resected (none
at margins, no lymph nodes). At least one of the following has
occured: a) penetration of the renal capsule
b) invasion of the renal sinus vessels
c)biopsy of tumor before removal
III- gross or microscopic residual tumor remains postoperatively
including inoperable tumor, tumor at surgical margins, tumor spillage
involving peritoneal surfaces, regional lymph node metastases or
transected tumor thrombus
IV- hematogenous metastases or lymph node metastases outside the
abdomen (lung, liver, bone, brain)
V – bilateral renal Wilms’tumor at onset

67. Treatment
• Preoperative chemotherapy > surgery> postoperative
chemotherapy with or without radiotherapy
• Primary surgery in infants less than 6 months old and in
adolescents (>15years)
• Prognosis
I stage 3year EFS 90%
II 85%
III 82%
IV 58%