1. NEUROBLASTOMA case
scenarios for plan mangment
Mustafa Mohamed Selim
NCI, Cairo University

2. 2
1
3
• Cases scenarios
• Treatment
• Relapse
• Late complications
• Epidemiology & genetics
• Clinical presentation
• Pathology, work up & staging
To put things on the map

4. Medicine
Can we
Should we
Ethics
Differance between 1

5. Ethics is doing what

6. The International Code of Medical Ethics
It declares that
“ A phsician shall act in the patients
best interest when providing medical
care”
2

7. Patient Case I

8. Patient Case I
• Katie is a 4-month-old healthy girl who is brought to
her pediatrician by her mother with a concern of
“projectile vomiting” for 3 days. Katie’s mother is
worried that she may have pyloric stenosis just as her
older brother did when he was an infant.
• The mother denies sick contacts. Urinary output has
been adequate, and Katie is gaining weight
adequately. Katie’s vital signs and physical
examination findings are normal.

9. What is the best investigation at this time ?
2. Reassurance
3. Pelvi abdominal us
1. cbc & chemistry (NA & K)
???

10. What is the best investigation at this time ?
2. Reassurance
3. Pelvi abdominal us
1. cbc & chemistry (NA & K)
???

11. Patient Case I
• A complete abdominal ultrasound is negative for
pyloric stenosis.
• However, it is positive for an incidental finding of a 2-
cm heterogeneous mass in the right retroperitoneal
space. The mass may be arising from the adrenal
gland, and it contains areas of calcification, with
partial vascularity on Doppler, and is not causing
mass effect.

12. What is the D.D of superarenal mass ?
???

13. What is the D.D of superarenal mass ?
???
1. Adrenal pseudocyst
2. Adrenal myelolipomas
3. Neuroblastoma
4. Lymphoma
5. Teratoma
6. Adrenocortical carcinoma

14. Patient Case I
• On consultation, a pediatric oncologist would like to see
Katie in her clinic today, with plans to obtain
investigations.

15. Pediatricians play a pivotal
role in the diagnosis of
neuroblastom
They should be aware of the
elusive signs and symptoms to
provide clinical surveillance
Appropriate referral, and
medical support as part of the
patient’s multidisciplinary team
Education Gap

16. ???

17. ???
1. A complete blood cell (CBC)
count,
2. Basic metabolic panel,
3. Liver enzyme levels,
4. Coagulation profile, and
5. Random urinary catecholamine
levels

18. ??? further

19. Low Risk Neuroblastoma:
1. Observation without biopsy
2. Surgery followed by observation
3. Chemotherapy with or without surgery
4. Radiation therapy
EFS
OS
> 90%
> 90%

20. Observation without biopsy
Treatment
• Small stage I or stage II adrenal masses
• Infants younger than 6 months
• Asymptomatic

21. Treatment - low risk NB
R• In recent years, clinical trials for infants with localized adrenal masses have
demonstrated excellent outcomes with observation alone.
• These masses tend to spontaneously regress, and can be observed without
surgical resection or chemotherapy.
• In a COG prospective trial observing infants less than 6-months old with
small adrenal masses,
 81% of subjects were effectively managed with expectant observation
alone,
 while the remaining 19% eventually underwent resection.
 None required chemotherapy.
 3-year EFS rates were 97% with OS rates of 100%.Nuchtern JG, London WB, Barnewolt CE, et al. A prospective study of expectant observation as primary therapy for
neuroblastoma in young infants: a Children’s Oncology Group study. Ann Surgery. 2012;256:573–580.

22. Treatment - low risk NB
R
• This strategy has become standard of practice, and the active COG ANBL1232
study (NCT02176967) has extended the age of observation for a subset of
localized tumors up to 12 months to determine whether observation alone is
appropriate in this age group as well.
• Infants with stage 4S/MS neuroblastoma may demonstrate spontaneous
regression, likely due to the unique biological features of neuroblastoma in
infants, including
 Near-triploid DNA content and
 Increases in expression of genes from the chromosome 1p36 region.
Lavarino C, Cheung N-K, Garcia I, et al. Specific gene expression profiles and chromosomal abnormalities are associated with
infant disseminated neuroblastoma. BMC Cancer. 2009;9:44.

23. ??? further
Observation without biopsy

24. Story
SELF-CONFIDENCE PRODUCES FINE RESULTS
Day 1
It was adapted from StefanSagmeister (importance of holiday)

25. Week 1
It was adapted from StefanSagmeister (importance of holiday)

26. Week 3
It was adapted from StefanSagmeister (importance of holiday)

27. Week 5
It was adapted from StefanSagmeister (importance of holiday)

28. K EEP
B E LIEVING
Y OURSELF

29. Patient Case II

30. Patient Case II
• Chase is a 3-year-old boy who presents
to the pediatrician’s office with
worsening hip pain, leg pain, and back
pain for 3 weeks. He has numbness in
both legs, and his mother has noted
shortness of breath when he is active.
Vital signs are normal in the office.

31. Patient Case II
• Significant physical examination
findings include decreased breath
sounds over the right lung and a large
non tender abdominal mass. Chase’s
gait is weak and altered, with
dragging of his right leg and frequent
falls when taking a few steps.

32. What is the best investigation at this time ?
2. Reassurance
3. Pelvi abdominal us
1. cbc & chemistry (NA & K)
???

33. What is the best investigation at this time ?
2. Reassurance
3. Pelvi abdominal us
1. cbc & chemistry (NA & K)
???

34. Patient Case II
• Laboratory results include a WBC count of
9,200/mL (9.2_x0001_109/L) with a normal
differential count, a hemoglobin level of 13.4
g/dL (134 g/L), and a platelet count of
420_x0001_103/mL (0.42_x0001_109/L). Electrolyte
levels are normal aside from an elevated
creatinine level of 1.2 mg/dL (106 mmol/L). Liver
enzyme levels and results of coagulation
studies are normal.

35. Patient Case II
• Emergency transport is arranged
to take Chase to a pediatric
hospital emergency department
because of concern for spinal cord
compression.

36. ??? further

38. ??? further
1. Dexa + iv fluids
2. MRI spine
3. Biopsy

39. It is an oncologic emergency & occured in 7-15 % in patients.
Neurologic recovery appears to be related to the severity of
presenting neurologic deficits.
Neurological manifestations of <4 weeks duration upon presentation
are usually reversible (Fawzy et al., 2014).
Spinal cord compression in NB can be effectively managed with
upfront chemotherapy.
Chemotherapy and laminectomy have equivalent overall survival
outcomes.
Spinal cord
compression
COMPLICATIONS

40. COMPLICATIONS
Initial surgical decompression should be reserved for benign
variants only, including ganglioneuroma.
RT is generally reserved for progressive symptoms despite
chemotherapy.
"In a review of 99 children with spinal cord involvement, 71 had
residual impairments after a median follow-up of eight years. The
most common impairments in this population were motor function,
scoliosis, and bladder function {Simon et al., 2012}"
Spinal cord
compression

41. Patient Case II
• Pathology:a stroma-poor, poorly
differentiated neuroblastoma.
Chemotherapy VS laminectomy ?

42. ??? further
Chemotherapy
VS
laminectomy

43. Patient Case III

44. Patient Case III
• Mohamed is a 4-year-old boy who presents to the
clinic with fever,fussiness, and decreased activity
for 2 weeks. Mohamed has lost (1 kg) since his last
visit 4 months ago. On physical examination
Mohamed is febrile [39.3°C] and tachycardic. He
appears pale and listless. He has bilateral cervical
lymphadenopathy, abdominal distention with
some tenderness, and petechiae on his extremities.
Mohamed refuses to stand and starts crying.

45. Patient Case III
• The CBC count shows a WBC count
of 3000/mL (3_x0001_109/L), with an
absolute neutrophil count of 800/mL
(0.80_x0001_109/L), a hemoglobin level
of 6 g/dL (60 g/L), and a platelet
count of 13_x0001_103/mL
(0.013_x0001_109/L).

46. Patient Case III
• A CT scan of the chest, abdomen, and
pelvis shows a large right adrenal mass
with widespread lymphadenopathy
notably in the right iliac chain, as well as
with the right inguinal lymph nodes. The
spleen is enlarged. The mIBG scan shows
extensive axial and appendicular skeletal
uptake

47. Patient Case III
• The oncologist performs bilateral BMA &
BMB, which show small clusters of round
blue cells, separated by a fibrillar matrix
(Homer-Wright rosettes). The small round
blue cells are atypical mononuclear cells
with irregular nuclei, clumped chromatin,
and mostly indistinct nucleoli.

48. What is the D.D of small round cells in BMA?
???

49. ???
What is the D.D of malignant small round cells in
BMA?

50. ??? further work up

51. Molecular studies
??? further work up

52. Patient Case III
▪ Molecular studies from the tumor biopsy
show MYCN amplification, gain of 17q, and
hypoploidy.
▪ Histopathologic review of the tumor and
lymph node biopsy samples demonstrate
a stroma-poor, poorly differentiated
neuroblastoma.

53. ??? TTT

54. High risk Neuroblastoma
~~EFS=50%
Induction Consolidation MaintenanceLocal control

55. High Risk Neuroblastoma

56. Each of the following is associated with poor
prognosis Neuroblastoma EXCEPT ?
2.TrkA gene activation
3. LOH at 1p36 and 11q23
1.N-myc amplification
MCQ
4.Telemorase epression and
increased teloere length

57. Each of the following is associated with poor
prognosis Neuroblastoma EXCEPT ?
2.TrkA gene activation
3. LOH at 1p36 and 11q23
1.N-myc amplification
MCQ
4.Telemorase epression and
increased teloere length

58. To which of the following events is good
outcome in neuroblastoma assochiated:
2. N-my amplification
3. Chromosome 1p deletion
1. Dioploidy
MCQ
4.TrK A expression

59. To which of the following events is good
outcome in neuroblastoma assochiated:
2. N-my amplification
3. Chromosome 1p deletion
1. Dioploidy
MCQ
4.TrK A expression

60. The most common malignant neoplasm of
infancy is:
2. Neuroblastoma
3.Wilms tumor
1. Malignant teratoma
MCQ
4. Hepatoblastoma

61. The most common malignant neoplasm of
infancy is:
2. Neuroblastoma
3.Wilms tumor
1. Malignant teratoma
MCQ
4. Hepatoblastoma

62. Cells from the neural crest are involved in all
except:
2. Neuroblastoma
3. Primitive neuroectodermal tumor
1. Hirschpruns disease
MCQ
4. Wilms tumor

63. Cells from the neural crest are involved in all
except:
2. Neuroblastoma
3. Primitive neuroectodermal tumor
1. Hirschpruns disease
MCQ
4. Wilms tumor

64. Which of the following malignant diseases of
children diseases of children has the best
prognosis:
2. Neuroblastoma
3. Rhabdomyosarcoma
1.Primitive neuroectodermal tumor
MCQ
4. Wilms tumor

65. Which of the following malignant diseases of
children diseases of children has the best
prognosis:
2. Neuroblastoma
3. Rhabdomyosarcoma
1.Primitive neuroectodermal tumor
MCQ
4. Wilms tumor

66. which of the following is the most common
inherited malignancy :
2. Neuroblastoma
3. Retinoblastoma
1.Infant leukemia
MCQ
4. Wilms tumor

67. which of the following is the most common
inherited malignancy :
2. Neuroblastoma
3. Retinoblastoma
1.Infant leukemia
MCQ
4. Wilms tumor

70. • Mustafa Mohamed Selim
• Pediatric Oncology Department (NCI)
• Assistant consultant (57357 CCHE)
• E.mial:(d_mostafaselim@hotmail.com)
• To download the presentation from
(www.slideshare.com) ~~ (Neuroblastoma presentation)