It is a slide on nephroblastoma. It talks about all you need to know about it.

1. NEPHROBLASTOMA & NEUROBLASTOMA
BY
EKENZE SEBASTIAN O. FWACS

2. NEPHROBLASTOMA
• Introduction
• Epidemiology
• Aetiology & Genetics
• Pathology
• Diagnosis
• Treatment

3. INTRODUCTION
• Osler 1879
• Wilms 1899
• Nephroblastoma (wilms tumor, WT) is the most common
malignant neoplasm in the urinary tract of children
• It is an embryonal renal neoplasm in which blastemal,
stromal and epithelial cell types are present.

4. EPIDEMIOLOGY
• WT represents about 6% of all childhood malignancies
• Reported incidence = 8 cases per million children/ year
• Here about 20 cases are seen / year
• 75% < 5 years
• Peak incidence = 2-3 years
• Male = female

5. AETIOLOGY & GENETICS
• The exact aetiology is unknown
• Recent studies point to genetic predisposition
• WT is sporadic in 95%; familial in 1-2%; bilateral in
5-10%
• 2% of WT associated with syndromes:
1. WAGR (WT, Aniridia, Genitourinary malformation, mental
Retardation)
2. Beckwith Wiedman syndrome (BWS) (Omphalocele, macroglossia
and visceromegaly)
3. Denys-Drash syndrome (WT, intersex disorder, nephropathy)
4. Perlman syndrome (Overgrowth syndrome with mental retardation)
• Other associated anomalies seen in WT: Isolated hemihypertrophy,
hypospadias, undescended testes.

6. • Children with such syndromes should be screened with ultrasound
every 6 months till 8 years of age.
• GENES involved in WT pathogenesis include:
* WT1 gene. Tumor suppressor gene located on 11p13; required for
normal kidney and gonadal development. Mutation of the gene seen in
WAGR, DDS, bilateral WT & 10% sporadic WT.
* WT2 gene. Located on 11p15; mutation in form of deletion or
overexpression is linked to familial WT and BWS.
* Additional WT loci include 16q, 1p, and p53 (located at 17p13.)
Mutation in these are associated with poor prognosis

7. PATHOLOGY
• MACROSCOPY: WT is sharply demarcated and variably encapsulated
with haemorrhagic areas and cavitations.
Location may be central or polar
• MICROSCOPY: 3 components seen in normal kidney differentiation---
blastema, tubules and stroma are present.
Based on microscopy, 2 broad variants are known:
1. Unfavorable histology. Presence of anaplasia– cells with nuclear
enlargement, hyperchromatic nuclei and abnormal mitotic figures.
Anaplasia is the single most important indicator of poor prognosis.
2. Favorable histology. WT without anaplastic features.

8. • STAGES. National Wilms Tumor Study Group NWTSG staging
system is universally accepted.
Stage I– Tumor limited to kidney and completely resected
II– Tumor extends beyond the kidney but is completely excised
III– Residual non-haematogenous tumor confined to the abdomen
IV– Haematogenous metastases
V– Bilateral tumor

9. DIAGNOSIS
History: Commonest is asymptomatic abdominal mass. Others include
abdominal pain, fever, weight loss, haematuria, anaemia, and varicocele.
WT may rupture and present as acute abdomen
Physical examination: Carefully palpate the abdomen, measure the blood
pressure, look into the eyes; and document anomalies if present.
Investigations: Should define the nature of abdominal mass; organ of origin;
status of the contralateral kidney; state of the vena cava; and distant
metastases.
* Ultrasound
* IVU
* CT scan
* Chest X ray
* Others: S/E/U/C, Full blood count.

10. TREATMENT
Involves surgical excision, post operative radiotherapy and chemotherapy.
This can be modified by: stage of disease, age of patient, size of tumor and
clinical state of patient.
Surgery:* serves to excise the tumor and determine intra abdominal stage.
* Important surgical caveats.
* Peculiar situations: IVC involvement, Bilateral tumors
*Complications: Haemorrhage, small bowel obstruction.
Chemotherapy:+ Mostly as adjuvant. Can be used as neoadjuvant in
inoperable tumor; non resectable tumor; bilateral tumor; and IVC
involvement.
+Agents: Actinomycin D, Vincristine, Adriamycin,
Cyclophosphamide.

11. Radiotherapy:* Same indication as chemotherapy.
* Renal bed demarcated by titanium clips placed during
surgery.
Treatment by stage
a. Unfavorable histology. All modalities for all stages
b. Favorable histology. Stages I & II, < 2 years--- SURGERY
> 2 “ -- SURG.+ CHEMO.
Stages III,IV,V– All modalities.
Results: Stage I = 96.5%
II = 92.2%
III =73%
IV/V/all unfavorable histology =68.1%

12. NEUROBLASTOMA
INTRODUCTION
- Wright 1910
- Tumor of neural crest origin
- May arise from the adrenal or the sympathetic ganglion from neck to pelvis
- Most common solid tumor in childhood
- Spontaneous regression and tumor maturation observed in a few cases
- Advances in management have not significantly improved outcome
EPIDEMIOLOGY
* Incidence= 1 in 8,000-10,000 children. Here = 1-2 cases/ year
* >50% are 2 years or less at diagnosis
* M > F 1.2 : 1.0

13. Pathology
Sites: 75% -- Retroperitoneal
50% Adrenal medulla
25% Paraspinal ganglia
20% -- Posterior mediastinum
5% -- Neck and Pelvis
Macroscopy: - Purple, highly vascular and friable.
- Becomes nodular as it matures or responds to therapy.
Microscopy: - Composed of neuroblasts– small round cell with prominent
nucleus and small cytoplasm.
- Immature tumor has no special arrangement of cells
- More mature tumor show rosette formation; some may
resemble normal ganglion cells.
Electron microscopy shows neurofibrils and electron dense granules; this
rules out PNET, rhabdomyosarcoma and Ewing’s tumor

14. Staging
Evans staging is commonly used.
Stage I - Tumor confined to the organ of origin
II - Tumor extends beyond the organ of origin but not crossing
midline. Ipsilateral nodes may be involved
III - Tumor extends beyond midline. Bilateral nodes may be involved
IV - Distant metastases
IVS- Same as I or II with presence of disease in the liver, skin or
bone marrow.

15. Aetiology & Genetics
Aetiology: Unknown.
Hereditary factors important
Cytogenetics/ Molecular biology: Alterations seen in NB are
1. Mutation at 1p36 – associated with poor outcome
2. Mutation at 14q
3. Amplification of N-myc protooncogene– poor prognosis
4. Expression of Multidrug resistant related protein gene and
bcl-2 gene activity--- poor outcome.
5. Expression of Nerve growth factor recceptors– good
prognosis

16. Diagnosis
Presentation: Related to the site of primary tumor; Metastases; and Metabolic
tumor products.
Common presentations include abdominal mass; weight loss; FTT; and anaemia.
Others: Respiratory distress, dysphagia, paraplegia, Horners syndrome,
hypertension, flushing & iritability, urinary sympyoms, constipation, skin
nodules, ‘panda eye’, watery diarrhea, dancing-eye syndrome etc.
Investigations: 1. Plain Xray
2. Ultrasonography
3. IVU
4.CT scan
5. Bone scan with MIBG
6. Urine chemistry: HMA= Undifferentiated NB; VMA= More
mature NB.
7.Blood chemistry: NSE, LDH, Ferritin
8. Immunohistochemistry: Neurofilament, NSE etc
9. Biopsy & Bone marrow aspiration
Others: LFT, FBC.

18. Tumor Markers
1. VMA/ HVA
2. Lactate dehydrogenase
3. Serum ferritin
4. Neuron-Specific Enolase NSE
5. Tumor derived gangloside GD2

19. Treatment
• Depends the stage at diagnosis
• Localized tumors are best managed with surgery
• Partially resected or unresectable tumors need CHEMO. & or RADIO.
• Surgery: Operative principles.
• Chemotherapy: Adjuvant or Neoadjuvant
Agents: Cyclophosphamide, Doxorubicin, Vincristine, Cisplatin.
Radiotherapy: For > 1 year olds. MIBG can be used.
Immunotherapy: IL-2 has been tried.
Treatment by stages
Stage I- SURG.
II- SURG + CHEMO
III- High CHEMO. then SURG.
IV- < 5 months- CHEMO then SURG
> 5 “ - High CHEMO or RAD. Then SURG, & High CHEMO
IVS- Supportive care

20. Outcome: Stage I – 90%
Stage II --80%
Stage III --60%
Stage IV --10%
Stage IVS --70%
Future: 1. Early diagnosis. Mass screening for VMA & HVA at 6 months
2. Use of differentiating agents e.g.13 cis – retinoic acid
3.Targetted Immunotherapy with anti ganglioside GD2 antibodies
for advanced NB.