Neuroblastoma

Introduction:
It is the second most common solid tumor in children after brain tumor. It occurs in the neural crest cells, called neuroblasts, of the sympathetic nervous system. It can occur in a number of anatomical sites. The majority of tumors (65%) are located in the abdomen, often in one of the two adrenal glands. However, primary tumors can occur anywhere in the body. Other common sites are the chest, neck or pelvis. It is one of the most malignant neoplasms of children & rarely seen in adults.

Incidence:
Neuroblastoma represents 7.5% of all childhood cancers. It is most commonly diagnosed between 17 months and 2 years of age.

Aetiology:
Neuroblastoma develops when normal neuroblasts (the immature cells of the sympathetic nervous system) fail to mature into nerve cells. Instead, they continue to grow leading to mass of cancer cells.

Other hypothesis is “mutations” occurring in Neuroblastoma cells.

Symptoms:
Symptoms of Neuroblastoma are dependent upon the site, metastatic disease or associated paraneoplastic syndromes,

Abdominal distention/constipation
Pain in the abdomen.
Fever, bony pain, anemia, if the disease has spread to the bone marrow, causing a decrease in red blood cells.
Bulging, darkening, proptosis or swelling of the eye, if the disease has spread to tissues and bone around the eyes.
Persistent diarrhea, high blood pressure, palpitations, reddening of the skin, sweating, involuntary movements of eyes & limbs, if there is associated paraneoplastic syndrome

Investigations:

Complete blood count
Biochemistry including serum LDH & serum ferritin
Bone marrow aspiration & Biopsy
Urinary VMA (Vanillyl mandelic acid) and HMV (Homovanillic acid)
N-myc amplification
DNA index
MIBG (131I-meta-iodobenzyl guanidine) scan
Chest X-Ray
CT Scan of primary region
MRI spine ( If neurological symptoms)
Bone scan
Biopsy of the tumor

Prognostic factors:

Age of the child
Stage of the disease
Tumor Histopathology
Myc-N Status
DNA Index (Ploidy)

Treatment:

Induction Chemotherapy: Multi-drug chemotherapy is first given to try to reduce the size of the primary and metastatic tumor(s). The drugs used are cyclophosphamide, doxorubicin, cisplatin, etoposide, Ifosphamide.

Surgery: Surgery is done to remove as much tumor as safely possible. In some locations its possible to remove whole mass

Radiation Therapy: It is usually given locally to the tumor site.

Myleoablative therapy followed by stem cell or bone marrow transplant: Intensive doses of chemotherapy to eliminate any remaining tumor cells, followed by an autologous peripheral blood stem cell transplant, or sometimes a bone marrow transplant, to restore the immune system is used in high risk disease.

Minimum residual disease therapy: Additional drugs like 13-cis-Retinoic acid, aimed at eliminating or altering minimal residual disease is given after consolidation therapy.

MIBG Therapy: It is used when surgery is not possible because of persistent bone marrow disease after induction chemotherapy.

Prognosis:

Low risk patients have a greater than 90% survival.
Intermediate risk patients have a 70-90% chance of survival.
High risk patients have a 30% chance of survival

Ewing Sarcoma

Introduction:
Bone tumors are sixth most common group of cancers in children. Two common types of primary bone cancers found in children are osteosarcoma & Ewing sarcoma. Ewing sarcoma is the second most common tumor of the bone. It most often affects bones of the pelvis, the tibia, fibula, and femur, and can also begin in the soft tissues. This disease most often occurs in second sdecade of life that is between the ages of 10 and 20.They are small round cell undifferentiated tumors.

Types:
These are the Ewing Family of tumors which include Ewing sarcoma and PNET (Primitive neuroectodermal Tumors.

Symptoms:
1. Pain at the site of tumor
2. Swelling at the site of tumor
3. Weight loss
4. Anorexia
5. fever, malaise
6. cough

Prognostic factors:
1. Site of the tumor
2. The presence of metastasis
3. Size of the tumor
4. Age
5. Erythrocyte Sedimentation rate
6. Serum LDH levels

Investigations:
1. Plain X-Ray of the local site
2. CT scan or MRI of the primary tumor
3. Chest X-Ray
4. CT of the chest
5. Bone scan
6. Bone marrow aspiration and bone marrow biopsy

Treatment:
Ewing sarcoma is treated with multimodality treatment.

1. Surgery:
The options are

Amputation
Rotationplasty
Limb salvage surgery

Surgery is not effective for treating metastatic disease.

2. Chemotherapy:
Chemotherapy uses drugs like Ifosfamide, Etoposide, Adriamycin, Vincristine, Cyclophosphamide.It may be used before surgery to shrink a tumor so that it can be removed surgically, and will be used after surgery for any remaining cancer cells.

3. Radiation therapy:
Ewing sarcoma is very sensitive to radiation.When surgery is not possible because of large tumor mass, metastatic disease, certain site of cancer then radiation therapy is an effective answer.

Retinoblastoma

Introduction
This is the most common primary tumor of the eye in children. It arises from the retina. .The retina is a layer of nerve tissue that coats the back of the eye, which is important for vision of person. Retinoblasts (immature cells of the retina) multiply during gestation and early life, to make enough cells to create the retina. As child grows, these cells mature & no longer differentiate. If these immature retinoblasts turn into cancer cells, retinoblastoma develops, the cause of which is unknown. The gene responsible is RB1 gene.

Incidence:
The annual incidence is one in 20000 children. It occurs most often in children under 4 years of age.

Types:
Hereditary:
•Hereditary form of Retinoblastoma occurs in 40%.
•May have more than one tumor
•Tumor often affects both eyes
•May have tumors in other parts of the body
•At increased risk for other cancers later in life

Non-hereditary:
•Most children with retinoblastoma (60%) do not have the genetic form.
•They develop tumor in only one eye i.e. unilateral.
•These children do not have an increased risk of developing other cancers.
•Their offspring have the same risk of developing retinoblastoma as other children in the population.

Symptoms:
•A pupil that looks white or red instead of the usual black i.e. called as white or cat’s eye reflex.
•A crossed eye i.e. strabismus.
•Poor vision
•A red, painful eye
•An enlarged pupil
•Differently colored irises

Investigations:
•Examination under general anesthesia using Retcam
•Ultrasound
•CT (CAT) scan
•MRI
•CSF examination
•Bone marrow studies
•Bone scan in advanced disease
•Chromosomal analysis (in certain cases)

Management:

1.Surgery to remove the eye, known as enucleation. This s done when there is no vision in eye to save further spread & life. Enucleation may also be recommended if the tumor does not respond to treatment.

2.Chemotherapy is used to shrink tumors in the eye. This approach is often used in children with bilateral disease (both eyes) for saving at least one eye which has less disease. It is also used in small tumors where the eye vision is present to save the eye. in combination with other measures such as

1.Photocoagulation--using laser light to destroy blood vessels supplying the tumor.
2.Thermotherapy--using heat to destroy tumor cells
3.Cryotherapy--using extreme cold to destroy tumor cells
4.Radiation Therapy—It is used for control of local disease with preservation of vision. Radiation plaque therapy and particle beam radiotherapy are used frequently.

Prognosis:
The five-year survival rate for children with retinoblastoma is more than 90%.