Neuroblastoma Staging System - To Classify The Disease
Neuroblastoma is classified into different stages
that aid in determining its prognosis. Staging
specifies whether the cancer has spread and if
yes, how far. This also helps to decide the
possible treatment options.
Stage 1
Tumour at this stage is completely resectable i.e
removable by surgery. The cancer has not spread to
other parts of the body and remains restricted to the
primary site of occurrence only.
Stage 2
Tumour at this stage cannot be completely removed
by surgery. It has not spread across the mid-line of the
body (spinel, but depending on the involvement of
lymph nodes, it is divided into two types: stage 2A and 2B.
Stage 2 A
The lymph nodes present on the tumour side do not
contain the cancerous tumour cells.
Stage 2 B
The lymph nodes present on the tumour side do
contain the cancerous tumour cells, while the lymph
nodes on the other side of the tumour do not comprise
of tumour cells.
Stage 3
This stage includes tumours that have spread across
the spine to the contralateral side or have contralateral
nodes involved. At this stage, the tumour cannot be
completely resected by surgery.
Stage 4S
This is the stage where the cancer cells have spread
from the initial site to other parts, i.e from spine to the
liver, skin and minimally to the bone marrow. This stage
occurs mostly in newborns below 1 year of age. Stage 4S
is also termed as "special neuroblastoma".
Stage 4
Here the cancer cells have metastasized to the
distant lymph nodes and organs which do not fulfill
45 stage.
Neural and Non-neural Mutual Associations
A variety of birth and developmental defects are present in
association with neuroblastoma. These can be either
neural or non-neural conditions.
Neuroblastoma tumour can be associated with
maldevelopment of neural crest tissues. This is evident by:
- Occurrence of Neuroblastoma tumours along with Von
Recklinghausen disease, which manifests as
development of noncancerous tumours on nerve and
skin
- Severe hypoglycemia, etc.
Neuroblastoma also occurs in association with non-neural
crest syndromes such as:
- Beckwith-Wiedemann syndrome (overgrowth disorder)
CHARGE syndrome - a condition which shows multiple
features like heart defects, growth retardation, genital
abnormalities, ear abnormalities, etc
Fetal and Infant Traits
Neuroblastoma is a malignant tumour representing a mass
on abdomen, neck, and other body parts. The clinical manifestations
of neuroblastoma depend upon the affected location and include
the following:
In the abdomen
- Swollen Abdomen (Abdominal mass and pain)
- Scrotal Mass
In the chest
- Inability to move, paralysis, weakness (cancers
compressing spinal cord)
- Breathing difficulties (due to tumour on chest)
- Hydrops Fetalis (abnormal accumulation of fluid in
fetal compartments)
- Unequal pupils, drooping eyelids, nerve damage in
neck (Horner's syndrome)
Other signs-
- Cutaneous metastasis (cancer growth on skin)
- Neurogenic Bladder (bladder dysfunction)
- Congenital chylothorax (accumulation of lymphatic
fluid in pleural cavity)
- Myoclonic encephalopathy (seizures, jerks, muscle
twitches)
- Bronchial obstruction from mediastinal tumour
' Bone pain
These neoplastic tumours are usually found as an unsuspected
detection in sonographs in prenatal
testings.
It is important to visit the pediatrician if you notice below symptoms
- Bulging eyes
- Dark circles around the eyes
- Bluish lumps under the skin
- Lumps in abdomen, neck, chest
- Easy bruising/bleeding
- Petechiae (red or purple spots on skin caused due to
broken capillary blood vessel of bleeding)
- Droopy eyelids, smaller pupils (Horner syndrome)
- Uncontrolled eye movements
Genetic Defects
Neuroblastoma tumour cells exhibit the following genetic features:
- Deletions of short arm of Chromosome 1
- Deletions of Long arm of Chromosome 119
- Extrachromosomal double minute chromatin bodies
- Homogeneously staining regions amplified with N-
mycgene
Neuroblastoma and N-myc amplification co-relations:
- Neuroblastoma cells which are found to have
amplification of N-myc gene also show abnormal
translocation of 17q chromosome.
- Patients in later stages of cancer show higher
amplifications of both the oncogenes N-myc and ras.
- The loss of heterozygosity of chromosome 1p is
associated with N-myc amplification.
- N-myc amplification is accountable for abnormal
histological patterns of the tumour cells.
N-myc amplification can evaluate increased expression
of Multidrug Resistant-Associated Protein (MDRAP)
gene, accounting for reduced survival. The estimation
of N-myc can therefore aid in the measurement of magnitude
of the disease depending upon the stage of the tumour,
as Stages 1 and 4S conveys single copy of N-myc gene, and
Stages 3 and 4 display multiple copies due to
genomic amplification.
How was your child diagnosed with neuroblastoma?
A. Blood and Urine Tests
1. Catecholamine Analysis - Most of the neuroblastomas
which are chemically active, secrete catecholamines (vanillmandelic -
acid and homovanillic acid mainly) in excess amounts than produced
by normal sympathetic nerve cells. Urinary catecholamine analysis will
aid in diagnosing neoplastic tumour and can also help detec
the possibility of recurrence.
2. Serum Ferritin - Cells of Neuroblastoma secrete
ferritin, elevating the serum ferritin levels which
interfere with the immune function of the
lymphocytes.
3. Serum Lactate Dehydrogenase (LDH) - LDH aids in
measuring tumour activity. Those with elevated levels
of LDH may have metastasis and tumour recurrences.
4. DNA Cytometric Analysis (DNA index) - Tumour cells
with aneuploidy have been associated with lower stage of disease
and are likely to support the initial stages of the treatment.
It helps to measure the percentage of tumour cells in the different
phases of the cell cycle, also allowing prediction of its prognosis.
B. Imaging Tests
These techniques help produce images and diagnose
masses in chest mediastinal masses), abdomen (flank masses),
ribs (rib erosion) due to primary neuroblastoma tumours, bone
metastasis, lytic lesions in skull, ribs, pelvis, etc. They also help
to measure the intraspinal extensions of neuroblastoma. The
imaging techniques that aid in diagnosis include:
1. Computed Tomography (PET-CT Scan) - It is a device that
uses X-rays to capture cross-sectional images of the different parts of the
body. The CT scanner takes rotational images from different angles
(horizontal and axial) instead of a single image. It helps in staging
the tumours of neuroblastoma and also helps identify its
organ of origin.
2. Magnetic Resonance Imaging (MRI) - Has the property
of multiplanar imaging. It helps to produce images of soft
tissues, especially of the brain and spinal cord. The
advantage of MRI scan is that it does not use ionizing
radiation. However, it cannot be used for children with
kidney diseases.
3."1 or "1-Metaiodobenzylguanidine ("l-mIBG)
Imaging-mIBG is a drug which is selectively taken
up by neural crest tumours such as neuroblastoma. ""'lmIBG
can also be used to give radionuclide therapy in
patients with widespread disease.
4. Tc-MDP (Methylenediphonate) Bone Scans - It helps
to identify the different bones which are affected by
tumour.
5. Ultrasonography - Neuroblastoma tumours appear as
echogenic masses which lack homogeneity. It helps in detecting
tumours in abdomen and pelvic region of the children. It also helps
to assess the size and extent of spread within the abdomen.
6. Positron Emission Tomography (PET) Scan.
Fluorodeoxyglucose (FDG) is a glucose analog which is
taken up by the cancer cells. FDG PET-CT Scan not only
help assess the spread of tumour to bones and abdomen
but also to other organs such as lungs, skin, bone
marrow and brain.
C. Biopsies
It is a procedure by which small samples of tissues are
collected and studied under microscope. The samples are
also sent for genetic testing.
Management and Treatment for Neuroblastoma
Neuroblastoma is curable but the survival rate depends
on the child's age, location of tumour and stage of the
tumour. Depending upon this, the survival is
approximated into different risk groups as below:
- Low risk groups (Stage 1 and 2) - Survival rate is higher
than 95%.
- Intermediate risk group (Stage 3) - Survival rate is about
90-95%.
- High risk group (stage 4) - Survival rate is lowered to
around 40-50%
The different types of treatments available include,
surgery, radiation therapy, chemotherapy, targeted therapy,
iodine 131-miBG therapy, immunotherapy, etc.
- Surgery is done in neuroblastoma to remove primary
tumour mass and regional lymph nodes.
- Radiation therapy is used to kill cancer cells so as to
prevent them from spreading. It is mostly used for
children who belong to lower risk groups.
- "'l-mlBG therapy is usually given to patients with
widespread disease. mlBG is selectively taken up by
cancer cells. The radioactive iodine (L-131) which is
tagged to it emits beta radiations which kills the cancer
cells.
- Chemotherapy involves administration of drugs in vein
which circulate in the body and kill the cancer cells.
Finding the ray of hope?
Cancer is like a nightmare that puts you into the clutches
of grief and affliction, and what can pull you back into the
battle called life is a 'ray of hope'. Nobody can understand
the depth of sorrow and the amount of confidence and
strength required to fight back, nobody but the one who
has been through it. What keeps you going in the times of
distress is the never giving up attitude, the family that
stands along the ups and downs, the conviction one gains
from the knowledge and awareness and advanced
science technology that will guide you in every step
through this journey. Ray of hope lies just one step ahead.
