Neuroblastoma & Wilms Tumour

Question 1

Define neuroblastoma

Answer 1

originates from neural crest cells to become a malignant, embryonal neuroendocrine neoplasm of the sympathetic nervous system that potentially secretes catecholamines so is usually found in the adrenal glands or sympathetic ganglia

Most common malignancy in infants 1-2 years old

Question 2

Etiology of neuroblastoma

Answer 2

The cause is unclear

Genetic associations:
Deletions of the short arm of chromosome 1 (1p deletion)
Causes overexpression of oncogene MYCN (N-myc)

Question 3

General Sx of neuroblastoma

Answer 3

Failure to thrive or weight loss
Fever
Nausea, vomiting, loss of appetite
Hypertension : by renal artery compression (unless part of a paraneoplastic syndrome that involves catecholamine secretion

Question 4

Local sx of neuroblastoma

Answer 4

Abdomen (60%)

• Palpable, irregular abdominal mass
• Abdominal distension and pain
• Hepatomegaly
• Constipation

Chest (20% ) (particularly paravertebral ganglia)
-Spinal cord compression → back pain, weakness, numbness, ataxia, loss of bowel or bladder control
Scoliosis
-Dyspnea, cough
-Inspiratory stridor

Neck
-Horner syndrome d/2 spinal cord compressions

Orbit of the eye

• Periorbital ecchymoses (“raccoon eyes”)
• Proptosis: protrusion of eyes d/2 increased orbital P

Bones

• Bone pain
• Anemia (bone marrow suppression)

Skin
-Subcutaneous nodules

Question 5

How is neuroblastoma dg

Answer 5

LAB
-Urine
↑ Catecholamine metabolites (HVA and VMA) in 24-hour urine

-BLOOD
↑ Catecholamine metabolites (HVA/VMA)
↑ LDH, ferritin, neuron-specific enolase (NSE)
(To track progression)
CBC with differential: anemia suggests bone met
Serum chemistry profile
Liver and kidney function tests

IMAGING
Abdominal ultrasound
CT or MRI: to identify the primary site
Scintigraphy w/MIBG scan:

BIOPSY
During surgical resection
Evaluated to MYCN gene amplification & DNA ploidy
Bilateral bone marrow biopsy of iliac crests for Met

Question 6

Why is MIBG scintigraphy Useful

Answer 6

MIBG is similar in structure to norepinephrine, so it is taken up by sympathetic nerve cells, including neuroblastoma or pheochromocytoma tumor

Question 7

What is the typical histology of neuroblastoma

Answer 7

1)Homer Wright rosettes:
Halo-like clusters of cells surrounding a central pale area containing neuropil-typical of neural tumors

2) Small round blue cells with hyperchromatic nuclei
3) Bombesin positive

Question 8

What is a bombesin

Answer 8

tumor marker for neuroblastoma, small cell carcinoma of the lung, pancreatic cancer, and gastric cancer.

Question 9

Dx of neuroblastoma

Answer 9

Wilms tumour

Pheochromocytoma

Osteomyelitis or transient synovitis

Question 10

How is neuroblastoma rx

Answer 10

According to their risk category (low, intermediate, or high),
based on :
1)neuroblastoma staging
2)age at diagnosis
3)presence/absence of MYCN amplification.

Question 11

What are the criteria for the stages of risk in neuroblastoma

Answer 11

Low risk:
early-stage disease (Stages 1–2)
no MYCN amplification

Intermediate risk:
intermediate and late-stage disease (Stages 3–4)
no MYCN amplification

High risk:
late-stage disease and/or MYCN amplification

Stage 4S (an exception):
disseminated disease in infants (< 12 months
low/intermediate-risk groups
unless they have a MYCN amplification, in which they are high-risk patients

Question 12

Rx for neuroblastoma according to risk level

Answer 12

Low risk

• observation
• Preop chemo @doxorubicin,cyclophosphamide, etoposide, and a platinum drug
• Surgery

Imdt risk

• preop chemo
• Postoperative chemotherapy
• Radiation: if surgery and chemo fails

High risk

• preop chemo
• Postoperative chemotherapy
• Radiation: if surgery and chemo fails
• target therapy
• MIGB therapy

Question 13

What is Wilms tumour

Answer 13

most common renal malig in children
affects children 2–5 years of age.

minority of cases are associated with specific syndromes (e.g., WAGR, Beckwith-Wiedemann) and gene mutations (e.g., WT1).

Question 14

Cause of wilms tumour

Answer 14

exact etiology remains unknown,

associated w/

GENETIC PREDISPOSITION
The WT1 (Wilms tumor 1) gene is the most important mutated in ∼ 10–20% of cases

ASSOCIATED SYNDROMES

1) Denys-Drash syndrome
- Wilms tumor
- Pseudohermaphroditism In makes -undescended testes due to gonadal dysgenesis
- Early-onset nephrotic syndrome

2)WAGR syndrome=deletion of several genes including WT1
-Wilms tumor
-Aniridia
-Genitourinary anomalies
@Pseudohermaphroditism @Early-onset nephrotic syndrome
-Retardation (Intellectual disability)

3) Beckwith-Wiedemann syndrome
- mutations of WT2 gene

Question 15

What are the sx if wilms tumour

Abdominal

General

Answer 15

Abdominal signs
-Abdominal mass:
Non-tender, Unilateral, doesn’t cross midline, Smooth and firm

-Abdominal pain

Other sx

• Hematuria
• hypertension
• HTN
• fever
• sx from metastatic spread

Question 16

Pathoanatomy of wilms

Answer 16

-consists of embryonic glomerular structures
Include cysts, hemorrhage, or necrosis. typically has a pseudocapsule.

-Classically made up of three different cell types, though some tumors may have two or just one of these types.

Question 17

Dx dg betw/ wilms and neuroblastoma

Answer 17

Fever & weight loss
-more common in NEUROBLASTOMA

calcifications on CT,vascular encasement, and/or midline crossing
-more common in NEUROBLASTOMA

123-MIBG scan & vanillylmandelic acid/homovanillic acid test

• Neuroblastoma positive
• Wilms tumor negative

Question 18

Rx of wilms tumour

Answer 18

Stage 1&2

• Nephrectomy
• Dactinomycin and vincristine chemo

Stage 3&4

• Nephrectomy
• Dactinomycin and vincristine chemo
• Doxorubicin
• Radiotherapy: Depends In lymph node involvement

Stage 5/ bilateral cases

• All of the above plus
• Preop chemo: vincristine,
• Renal parenchymal-sparing resection

Question 19

Prognosis of wilms tumour

Answer 19

Good prognosis: five-year survival rates up to 90%

Question 20

Can wilms tumour be prevented

Answer 20

Screening of WT1

Screening of syndromes