Common childhood tumors

1. Childhood Tumours
WACP Membership Revision Course
August 2020
Biobele J. Brown
Professor of Paediarics & Consultant Paediatrician
Dept. of Paediatrics
College of Medicine, University of Ibadan/ University College
Hospital Ibadan
1

2. Introduction
 Childhood cancer is relatively uncommon but among the
leading causes of death among children in industrialized
countries
 Important cause of mortality in developing countries
 While Acute Leukemia accounts for the majority of tumours
in Caucasians followed by CNS tumours
 In sub Saharan Africa, the Lymphomas predominate and in
particular Burkitt Lymphoma
2

3. Epidemiology
 Most tumour are commoner in males
 WT seems to have equal sex incidence
 Incidence of cancer 30 % higher in Caucasians than
blacks in US largest difference in ALL
 White and black children have approximately same
incidence of AML
 Hispanic children have higher rates of leukaemia than
white children
3

4. Aetiology
 In most cases unknown
 Factors-genetic
- environmental
4

5. Risk factors
Cancer Risk factors
Burkitt Malaria, EBV,
ALL Ionizing radiation, race (white>black),
genetics Down Syndrome, birth wt >4000g
AML Genetics
Brain cancers Therapeutic Ionizing irradiation to head
Hodgkin disease EBV, history in monozygotic twin
NHL Immunodeficiency,
osteosarcoma Ionizing irradiation, alkylating agents
Ewing’s sarcoma 9 X commoner in whites
5

6. Retinoblastoma gene
 The retinoblastoma gene RB-1 is located on chromosome
13q14
 Mutation predisposes to development of bilateral retinoblastoma
in the first year of life
 osteosarcomas and soft tissue sarcomas in later childhood and
adolescence
 adult tumours e.g. breast, bladder, prostate, cervical and small
cell lung carcinomas
6

7. Trisomy
 Trisomy 21 demonstrates predisposition to ALL and AML
 Acute megakaryoblastic leukaemia(AMKL) may be the most common type
of leukaemia seen in these patients
7

8. TP 53 gene
It is a transcription factor whose expression is increased
by DNA damage
 p53 blocks cell division at the G1 phase of the cell cycle
to allow DNA repair.
 TP53 is a tumor suppressor gene that provides
instructions for making, a protein called tumor protein 53
(TP53).
 The p53 tumor protein is located in the nucleus of cells
throughout the body and can bind directly to DNA
 When the DNA in a cell becomes damaged by agents
such as toxic chemicals or ultraviolet (UV) rays from
sunlight, this protein plays a critical role in determining
whether the DNA will be repaired or the cell will undergo
programmed cell death (apoptosis).
8

9. TP 53 contd.
 If the DNA can be repaired, p53 activates other genes to
fix the damage
 If the DNA cannot be repaired, the p53 tumor protein
prevents the cell from dividing and signals it to undergo
apoptosis
 This process prevents cells with mutated or damaged
DNA from dividing, which helps prevent the development
of tumors.
 Because the p53 tumor protein is essential for regulating
cell division, it has been nicknamed the "guardian of the
genome.“
 The human TP53 gene is located on the short (p) arm of
chromosome 17 at position 13.1
9

10. Li-Fraumeni syndrome
 Germ line mutation of one TP53 allele is found
in patients with Li-Fraumeni syndrome who
generally inherit a mutated TP53 gene from an
affected parent
 Patients with Li-Fraumeni syndrome are
predisposed to
 sarcomas
 breast cancer,
 brain tumours,
 adrenocortical cell carcinoma,
 acute leukemia;
 they have a 50% probability of cancer
development by age 30 years.
10

11. Investigations in suspected cancer
 FBC – for diagnosis and chemotherapy
 E/U, Cr, UA, Ca, P
 LFT’s
 CSF for cytology
 X-rays
 BM aspirate
 Abdominal USS
 CT Scan
 IVU
 MRI, MBIG, PET,
11

12. BURKITT LYMPHOMA
Named after Denis Parson Burkitt who mapped its peculiar
geographic distribution in Africa
 Commonest childhood malignancy in tropical Africa
 PATHOPHYSIOLOGY
 BL is a monoclonal proliferation of B-lymphocytes
characterized by
 Medium sized non-cleaved cells
 Gives a “Starry Sky” appearance on histology (also
observed in other highly proliferative lymphomas)
12

13. • Burkitt’s cells: monomorphic cells with round nuclei, multiple
nucleoli, and basophilic cytoplasm containing lipid vacuoles
• A starry-sky pattern is usually present, imparted by
numerous benign macrophages that have ingested apoptotic
tumour cells
• The rate of cell division is the highest of any known tumour
noted by the very high mitotic figures (Doubling time of 24
hours)
Pathology
13

14. Starry sky appearance
14

15. characteristics Endemic BL Sporadic BL HIV associated
BL
Epidemiology Equatorial Median age 30
yrs
HIV-risk groups
Median age 7yrs Median age 10-
19yrs
Associated with
malaria/climate
Clinical
presentation
Facial (50%) Abdominal, ileo-
caecal (80%)
Nodal and
extranodal mostly
abdomen
CNS (33%) Bone marrow
(20%)
Other organs also
affected
Other organs also
affected
Geographic
regions
Equatorial Africa,
Papua New
Guinea
N. America, N and
E Europe and far
East
Endemic HIV
areas in Africa
EBV association 100% 30% 30-50%
15

16.  BL is more common in Eastern Africa as compared to other
African countries where malaria is endemic
 Occurs in areas where
 the mean temperature >16°C
 where altitude was less than 5000 feet above sea level
 and annual rainfall more than 50 cm.
• Area of highest risk: between 10° north and 10° south of the
equator and in Papua New Guinea
 Between 19 and 36% of childhood cancers in high-risk areas
are accounted for by BL (e.g. Malawi, Nigeria, Uganda and
Papua New Guinea)
 [de Thé G. E IARC; 1985. p. 165-76].
Epidemiology of Endemic BL
16

17.  Chromosomal rearrangement of the proto-oncogene c-MYC is the genetic
hallmark of BL
 Over 80% of BL cases have a translocation of MYC at band q24 from
chromosome 8 to the Ig heavy chain regions on chromosome 14(q32),
t(8;14).
 Less frequently rearrangements translocate c-MYC to a position
 close to one of the light-chain loci on chromosome 2 (kappa light chain)
[t(8;2)] or chromosome 22 (lambda light chain) [t(8;22)].
 As a consequence of these translocations, the proto-oncogene
 C-myc, or at least its coding position, is joined with the Ig loci.
 This may lead to the activation of the proliferative role of C-myc by
deregulating its expression, although the factors involved in this process are
still controversial.
Genetics
17

18.  The role of P. falciparum in the development of BL has
been suggested by the shared geographic distribution of
eBL and holoendemic malaria.
 Endemic BL outside Africa is seen in other malaria
holoendemic areas such as Papua New Guinea while it
is also observed in Brazil where malaria is not
holoendemic
Malaria
18

19.  (1) During infancy, Epstein-Barr virus (EBV) infection
 (2) It drives B cell expansion, which is held in check by T
cell immune function unless malaria or AIDS ensues
 (3). Afterward, the expanded B cell pool is prone to a
chromosomal translocation
 (4) that brings the c-MYC oncogene under the
governance of an immunoglobulin gene t(8;14)
 (5) which leads to unbridled cell proliferation
Hypothesis of BL
pathogenesis
19

20.  In adults, 3-fold increase in BL (66% HIV+) between
1992-1996 was reported in a survey in Kenya
 In children, BL is still more likely to be of the endemic
form than the one associated to HIV, as shown by two
studies from Uganda, although another study has
identified a strong association between HIV and BL in
children in Kampala
 Poor survival of children infected with HIV perinatally
has been suggested as one of the explanations for the
lack of association found in some studies.
Occurrence of HIV associated BL
20

21. BL- Clinical Features
 Male: female ratio is 2:1
 Age: affects children between 2 and 16 years. Mean age in
 Africa is 7 years
 Jaw: swelling, loosening of teeth, proptosis
 Abdominal masses- kidneys, ovary, ascites
 Most cases in Ibadan are abdominal
 Renal impairment from tumour lysis syndrome
 Rare cases may present as acute leukaemia ( L3-ALL)
 CNS: paralysis( usually flaccid), cranial nerve palsies
21

22. BL- Investigations
 FBC,
 X-ray jaw: loss of dental lamina dura, osteolytic
lesions, dental mal-alignment
Other causes of loss of dental lamina dura
- hyperparathyrodism, rickets, leukaemia, following dental
extraction, myelomatosis, Cushing’s disease, idiopathic
osteomalacia, idiopathic chronic familial hyperphosphatemia
22

23. Other Burkitt’s Investigations
 E/U, Cr, Ca, P, uric acid, Liver function tests
 FNAC or Biopsy
 Abdominal USS for abdominal masses
 CSF cytology- mandatory, ascitic or pleural fluid
cytology
 Bone marrow aspiration or biopsy- mandatory
 Chest Radiograph
 CT-Scan or MRI of primary site
 Fluorine-18-2-fluorodeoxy glucose (FDG)- PET is an
imaging modality using physiological tracer glucose
whose uptake is increased in tumour cells – useful in
staging, monitoring lymphomas
23

24. STAGING( NCI)
 A – solitary extra abdominal site
 AR – completely (>90%) resected intra
abdominal tumour
 B – multiple extraabdominal sites
 C – intra abdominal tumour + facial tumour
 D – intra abdominal tumour + sites other than
facial
24

25. TREATMENT
 Chemotherapy is mainstay
 Options
COM-cyclophosphamide, vincristine, methotrexate
CNS prophylaxis is essential: IT MTX or ARA-C
Other regimens include
CHOP- doxorubicin replaces methotrexate
CHOP and Methotrexate (MTX)
CODOX-M/IVAC Regimen (Magrath Regimen)
Prophylactic allopurinol and aggressive hydration should
start as soon as BL is diagnosed
25

26. prognosis
 Stages A and AR have survival rate > 90%
 Bone marrow, CNS, peripheral blood manifestation, age
over 13 years at diagnosis, Stage D - all confer poor
prognosis
 Most regress with chemo but relapse is common 80-95%
survival in some reports
 INCTR Protocol COM + IT therapy, salvage IEC (Ifosfamide,
Etoposide, Cytarabine) : overall survival of 67% and 62% at
1 yr and 2 yrs respectively
26

27. Hodgkin Lymphoma
 Progressive painless enlargement of lymph nodes
 Childhood form – under 15yrs
 unusual < 5yrs
 CF: lymphadenopathy in 90% of cases
 Systemic symptoms (B symptoms) considered important
in staging are
 unexplained fever >39°C, weight loss >10% total body
weight over 3 mo, or drenching night sweats.
 Less common symptoms are pruritus, lethargy, anorexia,
27

28. Pathology
 EBV
 REAL classification
 2 classes
 Nodular lymphocyte predominant
 Classical HD
 Classical has 4 histologic subtypes
 Lymphocyte rich,
 Nodular Sclerosis ( most common)
 Mixed Cellularity
 Lymphocyte Depletion
 Reed-Sternberg cell,
 others lymphocytes, histiocytes, plasma cells
28

29. Diagnosis and Treatment of HD
 DIAGNOSIS – LN Biopsy
 Other for staging – FBC, LFT, CXR,
 Imaging Abd/Chest, B marrow
 TREATMENT
 Chemotherapy – MOPP: Nitrogen Mustard, Oncovin,
Procarbazine, Prednisone
 ABVD(Adriamycin, Bleomycin, Vinblastine, Dacarbazine),
COPP ( cyclophosphamide, vincrisitne, procarbazine,
prednisone)
 Radiotherapy
29

30. NON – HODGKIN LYMPHOMA
 Age: 5-15yrs M>F
 Abd
 - nodal
Extranodal – GIT (intusscep >6yrs)
 Mediastinum
 Head and neck
 Peripheral nodes
 Other sites-bone, breast, gonads, orbit, skin
30

31. Treatment of NHL
 Sub types
 DLBCL, Burkitt, Lymphoblastic, ALCL
 Standard treatment is Chemotherapy
 CHOP [Cyclophosphamide, hydroxorubicin
(doxorubicin), Vincristine, Prednisolone]
 Rituximab in B cell NHL (CD20+ tumours)
 + Irradiation
 + surgery
31

32. RETINOBLASTOMA
 Malignant congenital tumour of the embryonic neural retina
 Most common intraocular tumour of childhood
 60% of cases non-hereditary and unilateral
 15% of cases hereditary and unilateral
 25% of cases hereditary and bilateral
 MOLECULAR GENETICS
 RB maps to chromosome 13 band q14
 RB1 is inherited in an autosomal dominant fashion
 Individuals with heritable RB have a high risk of 2nd
malignancies e.g. osteosarcoma, soft tissue sarcoma
32

33. Clinical Features
 Bilateral RB is diagnosed at a median age of 14 mo and
unilateral disease at a median age of 23 months
 Most common features
 Leucocoria with a white pupillary reflex
 Strabismus
 Red painful eye
 TRILATERAL RETINOBLASTOMA
 Consists of solitary midline intracranial retinoblastoma
(usually pineal) that occurs usually in association with
heritable RB ( usually 10 yrs interval)
33

34. Diagnosis
 Dilated fundoscopic examination under sedation or general
anaesthesia is essential
 Extent of tumour further defined by
 USS
 CT Scan of brain and orbit
 MRI of brain and orbit
 TREATMENT
 Depends on extent and CNS involvement
34

35. Retinoblastoma- treatment
 Modalities for intraocular disease include
 External beam radiotherapy
 Episcleral plaque therapy
 Laser Photocoagulation
 Cryotherapy
 Thermotherapy
 Enucleation
 A combination of these modalities
 Chemotherapy : Vincristine, Etoposide, Carboplatin(VEC)
35

36. NEUROBLASTOMA
 Originates from primordial neural crest cell that normally
give rise to the adrenal medulla and sympathetic ganglia
 INCIDENCE
 Most common tumour in infancy
 Accounts for 7% of childhood malignancies
 At diagnosis 75% of cases are under 4 years
 Peak incidence 2 years
 CLINICAL FEATURES
 Head and Neck: unilateral palpable mass, Horner syndrome
 Orbit and eyes: Orbital secondaries with periorbital
haemorrhage(“racoon eyes”)
36

37. Neuroblastoma-2
 Exophthalmos, supraorbital masses, ecchymosis,
opsoclonus ( dancing eye syndrome)
 Chest: dyspnoea, pulmonary infections, dysphagia
 Abdomen: over 60% of cases arise from the abdomen
Mass usually crosses the midline
massive involvement of the liver with metastatic disease
(Pepper syndrome)
pelvis : constipation, urinary retention
paraspinal area: dumb bell or hour glass shaped
neuroblastoma
-paraplegia, weakness of lower limbs
Bone- pain and limping (Hutchinson’s syndrome)
Lungs – rare
37

38. Neuroblastoma-3
 Paraneoplastic manifestations
features of excessive cathecolamine secretion – intermittent
attacks of sweating and flushing, headaches, palpitation,
Hypertension (renin induced) : 1-5% of patients
Kerner-Morrison syndrome: VIP secretion leading to
intractible watery diarrhoea. FTT, abd distention,
hypokalemia
38

39. Neuroblastoma-diagnosis 4
 Abdominal USS- multiple or single masses with downward
and lateral displacement of the kidney
 usually calyceal architecture is preserved on IVU
 Minimal criteria for diagnosis are either
 1. Pathologic diagnosis from tissue by light microscopy ±
immunohistochemistry and/or increased urine or serum
cathecolamines VMA or HVA
 2. Bone marrow biopsy showing unequivocal tumour cells
+ Increased serum or urine cathecolamines
24hr urine vs spot urine/cr ratio: children 2-12 mg VMA/g
creatinine in urine
39

40. TREATMENT
 Urinary VMA/HVA increased in 90 %
 Urinary VMA/Cr
 Treatment
 Surgery- for early stage
 Multi-agent chemotherapy- for advanced stages.
 The most commonly used drugs are cisplatin,
doxorubicin, Cyclophosphamide, teniposide and
etoposide
CCG-3891: cisplatin, doxo, etop, cyclophos
 High dose consolidation chemo with autologous Stem cell
rescue
40

41. PROGNOSIS
 Age – younger better <1yr
 Site: Abdomen worse
 Stage
 Pathology – less differentiated is worse
 Stage 4S (liver, skin, marrow in child <1yr old)
 MYCN gene amplification
41

42. WILMS TUMOUR
 Most common primary malignant renal tumour of childhood
 Equal prevalence in boys and girls
 78% of children diagnosed at 1-4 years
 Peak 3-4 years
 Usually sporadic but familial in 1% of cases
 WT1 the Wilms’ tumour gene, is located on chromosome 11
band p13
 5-10% of Wilms tumours have demonstrable homozygous WT1
mutations
 These mutations have been demonstrated in individuals with
WAGR syndrome and Denys-Drash syndrome
 CONGENITAL ABNORMALITIES
 Congenital abnormalities occur in 12-15% of cases
 Include aniridia, hemihypertrophy, Beckwith-Wiedermann
syndrome
42

43. WT - 2
 Genitourinary tract anomalies including WAGR syndrome
(WT, aniridia, genito urinary malformations and mental
Retardation
 Denys - Drash ( WT, nephropathy, genital abnormalities)
 examples of anomalies- horse shoe kidney, dysplasia of
kidneys
 cystic disease of kidneys, hypospadias, cryptorchidism,
duplication of collecting system, club foot
CLINICAL FEATURES
 FLANK MASS that usually does not cross the midline
 Haematuria- more often microscopic
43

44. Clinical features of WT
 FLANK MASS that usually does not cross the midline
 Usually painless ( may be painful with haemorrhage)
 Haematuria- more often microscopic
 Haematuria
 Hypertension- 25 % of patients
 Polycythaemia
44

45. WT- Imaging
 USS now initial radiographic evaluation
 WTs are generally over 10cm in diameter at diagnosis
 Dilatation of collecting systems, focal areas of necrosis and
 Haemorrhage may be seen
 Calcification -5-10% of cases
 Rarely cystic
 Tumour may extend into renal vein
 Most common site of haematogenous metastasis is the lung
 IVU-distorted calyces, impaired or non-excretion of the dye
 Serum carcino-embryonic antigen is elevated
45

46. Treatment
 Depends on stage
 Required for you to know the staging NWTS
 Nephrectomy + chemotherapy + radiotherapy
 Chemotherapeutic drugs include vincristine, actinomycin D,
Doxorubicin
 Usually 24 wk of Rx
 PROGNOSIS
 Histology –favourable vs unfavourable (anaplasia)
 Age – younger better <2yrs
 Extent – stage
46

47. Beckwith-Wiedemann syndrome
 Associated with increased incidence of
 Wilms’ Tumour
 Neuroblastoma
 Rhabdomyosarcoma
 Adrenal carcinoma
 Hepatoblastoma
47

48. Acute Leukaemias
 Acute leukaemias represent a clonal expansion and arrest
at a specific stage of normal myeloid or lymphoid
haematopoiesis
 Account for 97% of childhood leukaemias and consist of
 1. Acute lymphoblastic Leukaemia-75%
 2. Acute myeloblastic “ -20%
3. Acute undifferentiated leukaemias <0.5 %
4. Acute mixed lineage leukaemia (AMLL)
INCIDENCE
peak between 2 and 5 years
48

49. Leukaemia- Aetiology
 Aetiology unknown but the following are important in the
pathogenesis
 1. Ionizing radiation
 2. Chemicals ( benzene)
 3. Drugs ( alkylating agents)
 4. Genetic considerations
Down syndrome, Bloom Syndrome, Blackfan-Diamond
syndrome
49

50. Cytochemical characteristics
ALL AML
PAS Present as coarse
granules or blocks in
a variable no of cells
Negative or diffusely
positive
Sudan Black Negative Positive
Peroxidase Negative Positive
Alkaline
phosphatase
Normal Low
Naphthol AS-D
Chloroacetate
Negative Positive
Naphthol AS-D
acetate
Negative or weakly
positive
Positive
α naphthyl acetate negative negative
Acid phosphatase Positive in T ALL negative
50

51. Acute lymphoblastic Leukaemia- Clinical
Features
 General – fever (60%) , lassitude (50%), pallor (40%)
 Bone marrow invasion-
 anaemia- pallor, tachycardia
 neutropenia- fever, infection,thrombocytopenia
 Lymphoid system invasion – lymphadenopathy,
hepatosplenomegaly
 Extramedullary invasion-
 CNS- raised ICP, cr nerve palsies, haemorrhage,
chloromas (retro-orbital deposits , spinal cord)
 Others: testes,ovaries, kidneys, bones, joints,
lungs
51

52. Clinical features of ALL
features Percentage of patients
fever 61
bleeding 48
Bone pain 23
lymphadenopathy 50
splenomegaly 63
hepatospenomegaly 68
52

53. Laboratory findings ALL
Laboratory features Percentage of
patients
WBC count/ cmm
<10,000 53
10,000 -49,000 30
>50,000 17
Haemoglobin g/dL
<7.0 43
7.0-11.0 45
>11.0 12
Platelet count/cmm
<20,000 28
20,000-99,000 47
>100,000 25
Lymphoblast
morphology
L1 84
L2 15
L3 1
53

54. ALL classification
 Morphology : FAB
 Immunology:
 B 85%
 T 15%
54

55. Leukaemias - Diagnosis
 Blood count
 Hb is low
 WBC low, normal or increased
 Platelets low in 92% of cases
 Blood smear- blasts
 Diagnosis confirmed with bone marrow aspirate or biopsy
 ALL : Blasts > 25%
 AML : Blasts >20 % or clonal cytogenetic abnormalities
irrespective of blast count (WHO). E.g. t(8:21) (q22:q22)
 TRE ATMENT
 CHEMOTHERAPY
55

56. Treatment of ALL
 Standard Risk
 Induction of remission ( Vincristine,
corticosteroid, PEG Asparaginase)
 Consolidation (intensification) of remission
 Interim maintenance
 Delayed intensification
 Prevention of overt CNS leukaemia
 Maintenance therapy ( M;32 mo, F :20 mo)
Overall :Duration- 2 yr in girls and 3 yr in boys
56

57. Prognostic factors in childhood ALL
Factor Favourable Intermediate Unfavourable
Age (yr) 1-9 ≥ 10 < 1and MLL+
WBC count <50,000/μL ≥ 50,000/μL
Immunophenot
ype
Precursor B
cell
T cell
Genetics Hyperdiploidy
Chromosome
s or DNA
index>1.16
Trisomies
4,10,17
t(12:21)/ETV
6-CBFA2
Diploid
t(1:19)/TCF3-
PBX1
t(9:22)/BCR-
ABL1
t(4:11)/MLL-
AF4
Hypodiploid <
44
chromosomes
CNS status CNS 1 CNS2 CNS 3
MRD <0.01 0.01 to 0.99% ≥ 1%
57

58. Acute myeloblastic leukaemia
 CF: similar to ALL
 Others: Chloromas, scalp swellings, gingival
hyperplasia
 Classification
 WHO
 FAB: M0-M7
 M7 Megakaryoblastic leukaemia frequently
observed in Trisomy 21
Tx: Daunorubicin, Ara-C, Etoposide (DAE)
Stem cell transplant
58

59. Treatment of M3
 Treatment of acute propmyelocytic
leukaemia(APML) with trans-retinoic acid is
useful in induction of remission
 FISH performed on blood or bone marrow is
identifies the chromosomal translocation
(t[15;17]) that characterizes APML
 Remission: <5 % blasts in a normocellular
marrow with trilineage recovery of peripheral
blood counts and no evidence of leukaemia at
other sites
59

60. Prognostic factors AML
 Age: not a consistent prognostic factor
 Race: Caucasians better than African-
Americans
 Poor prognosis
 Monosomy 7
 WBC count> 100,000/cmm
 Secondary AML
 Poor outcome: M7 patients without Down
syndrome
Recent studies suggest good outcome with M3
60

61. Prognosis AML
 Chemotherapy alone cure 50%
 Chemotherapy+ bone marrow transplantation cures 70%
 Children with AML with Down Syndrome have good cure
rate > 80% with chemotherapy alone
 Relapse associated with poor prognosis
61

62. CNS tumours
PATHOLOGY
Majority arise from glial cells e.g. astrocytomas,
ependymomas
They tend not to metastasize outside the CNS
unless there is operative intervention
There is an association with neurofibromatosis,
tuberous sclerosis, Li-Fraumeni syndrome
62

63. CNS tumours -Classification
 Supratentorial lesions-
 1. cerebral hemisphere:astrocytoma,ependymoma,
glioblastoma, meningioma
 2. Sellar or chiasm: craniopharyngioma, pituitary
adenoma,optic nerve glioma
 Infratentorial lesions-
 1. cerebellum:meduloblastoma, astrocytoma, meningioma,
 2. brain stem- astrocytoma, ependymoma, glioblastoma
63

64. CNS- Clinical features
CLINICAL FEATURES
>50% in the posterior fossa generally i.e. infratentorial
Children under 5 years of age have the greatest incidence of
brain tumours.
1/3 of all paediatric brain tumours present before the age of
5, and 3/4 before age 10
Symptoms and signs depend on histological xteristics
and rate of growth
>Focal neurological deficit
>ICP
64

65. CNS clinical features -2
Mental disturbances-somnolence, irritability,
personality changes
Vomiting
Diplopia/head tilting
impaired vision
 seizures( usually focal)
 disturbances of gait and balance
 endocrine abnormalities
 diencephalic syndrome( sudden FTT and emaciation
caused by hypothalamic tumour
65

66. CNS tumours - investigations
X-RAYS
• Plain
• Angiography
CT Scan / MRI
CSF cytology
TREATMENT
Surgery
Radiotherapy
Combination chemotherapy
66

67. Rhabdomyosarcoma
Arises from same embryonic mesenchyme as striated
muscle
Commonest of the soft tissue sarcomas
Age: all ages peak 2-6yrs, 15-19yrs
M : F ratio is 1.1:1 to 1.5:1
May be associated with neurofibromatosis (as in malignant
triton tumour)
Histology
Embryonal (57%) head,neck, orbit, GUT
Botryoid variant bladder, vagina, nasopharynx
Spindle cell variant paratesticular
Alveolar (24%) adolescents, extremities, trunk
67

68. Rhabdomyosarcoma - 2
CLINICAL FEATURES
Head and neck 40%
Extremities 20%
GUT 20%
Trunk 10%
Retroperitoneum
GIT
Botyroides Rhabdomyosarcoma: grape-like tumour
projecting into body cavity e.g. vagina, uterus, bladder,
nasopharynx
68

69. Rhabdomyosarcoma - 3
 Head and neck
 Orbit
 Parameningeal (nasopharynx, middle ear, paranasal
sinuses, infratemporal and pterygopalatine fossa
 Others- larynx, oropharynx, parotid, cheek, scalp, oral
cavity
TREATMENT
Surgery
Radiotherapy
Chemotherapy (VAC- Vincristine, Actinomycin D,
cyclophosphamide)
69

70. Hepatoblastoma
 Hepatic neoplasm
 80% occur in children < 3yrs
 Very low birth weight infants at increased risk
 Associated congenital abnormalities: hemiphypertrophy,
Beckwith-Widemann syndrome
 CF: upper abd mass, abdominal enlargement, anorexia,
weight loss
 Most cases arise from right lobe
 Investigagtions: Abd USS, biopsy
 LFTs- abnormal in 15-30%
 AFP: elevated in 60-70%
 Treatment: Surgery,
 chemo therapy: cisplatin, vincristine, doxorubicin,
fluorouracil
70

71. ONCOLOGIC EMERGENCIES
CLASSIFICATION
Based on anatomical region
 Thoracic emergencies
 CNS emergencies
 Abdominal emergencies
 Metabolic and Endocrine emergencies
 Hematologic emergencies
71

72. THORACIC EMERGENCIES
 Superior vena cava syndrome
 Superior mediastinal syndrome
CAUSES
A. Intrinsic
 Occlusion of central venous catheter
B.Extrinsic
 Hodgkin lymphoma
 Non-Hodgkin lymphoma especially lymphoblastic
lymphoma or large cell lymphoma
72

73. CNS EMERGENCIES
 Spinal cord compression
 ↑ICP
 Brain herniation
SPINAL CORD COMPRESSION
 4% of children with cancer develop acute spinal or
cauda equina compression
 Sarcoma 50%
 Neuroblastoma
 Lymphoma the rest
 Leukaemia
73

74. TREATMENT
 For Spinal cord compression and SVCS or SMS
 Has to be started immediately => emergency
 Potential for permanent neurological damage high
 Dexamethasone
 loading dose 10mg then 4mg 6 hourly
If mild stable deficits, 0.25-1mg/kg/day 6 hourly
74

75. METABOLIC AND ENDOCRINE
EMERGENCIES
A) HYPERLEUCOCYTOSIS
B) TUMOR LYSIS SYNDROME
C) SYNDROME OF INAPPROPRIATE ADH
SECRETION
D) HYPERCALCEMIA
75

76. Hyperleucocytosis
WBC >100,000/cmm
CML>AML>ALL
Leukostasis, thrombosis and secondary
haemorrhage
CF:
CNS: blurred vision, delirium, haemorrhage
Pulmonary: dyspnoea, pulmonary infiltrates
GUS: oliguria, priapism
Vascular: renal vein thrombosis, DIC, MI, retinal
haemorrhage
76

77. Hyperleucocytosis Rx
- Hydration and Alkalinization IVF 5% D in 1/5
saline + 50 – 100meq/L NaHCo3 @ 2-4 x
maintenance.
- Mannitol 0.5 – 1g/kg (for oliguria unresponsive
to hydration and frusemide)
77

78. Hyperleucocytosis Treatment contd
- Allopurinol 100mg/m2/dose 8hrly
- Leucophoresis / Exchange Transfusion
- Platelet tranfusion
- Avoid blood tranfusion and diuretics (keep PCV
≤ 30%).
- Chemotherapy
- Dialysis
78

79. Abdominal emergencies
 Esophagitis
 Gastric haemorrhage
 Typhilitis
 Peri-rectal abscess
 Haemorrhagic pancreatitis
 Massive hepatic enlargement from tumour
79

80. Tumour lysis syndrome
 Syndrome of metabolic abnormalities
 Results from spontaneous or treatment related tumour
necrosis
 May occur 1-5 days following initiation of chemo
 Large tumour burden e.g. leukaemias, Burkitt lymphoma
 Hyperkalemia (≥ 6 mEq/L)
 Hyperphosphatemia (> 6.5mg/dL)
 Hypocalcemia (ionized calcium < 1.5mEq/L)
 Hyperuricamia (>8mg/dL)
 Increase in values by 25% within 3 days before or 7 days
after initiation of therapy
 Uric acid nephrophathy, Acute kidney injury
80

81. Cairo and Bishop
classification
 Tumor lysis syndrome can be classified as laboratory or
clinical.
 In laboratory tumor lysis syndrome, two or more
metabolic abnormalities must be present during the same
24-hour period within 3 days before the start of therapy or
up to 7 days afterward.
 Clinical tumor lysis syndrome:
 laboratory tumor lysis syndrome plus an increased
creatinine level, seizures, cardiac dysrhythmia, or death.
81

82. Mx of Tumour Lysis Syndrome
 Prevention: hydration/Allopurinol
 Hydration: 2-4X maintenance fluid or 3-5L/m2 SA per day
 Alkalization – risk of hypocalcemia, nephrocalcinosis
 Allopurinol (xanthine oxidase inhibitor)
 Rasburicase: catalyzes uric acid to its water soluble metabolite-
allantoin
Correct serum P through Hydration, Phosphate binders (e.g. Ca
Carbonate or acetate), saline diuresis
Avoid Ca admin if possible (as Ca:P product approaches 60,
metastatic calcification can worsen renal damage)
82

83. Turmour Lysis Syndrome Monitoring
 Strictly monitor I/O, Urine S.G. and pH
 Aim for urine S.G. <1.010, output > 100ml/m2/hr
 Urine pH 6.5-7.5
 Monitor E/U, Cr, UA, Ca, P every 6 hrs
 Cardiac monitor if Hyperkalemia or hypocalcemia
present
83

84. Thank you for your attention
84