NEUROBLASTOMA

Issah J. kiswagala

(M.B.B.S).

INTRODUCTION

• Neuroblastoma is the most common extra-cranial solid tumor of infancy.
• It is an embryonal malignancy of the sympathetic nervous system arising from neuroblasts.
• In the developing embryo these cells migrate along the neuraxis, and populate the sympathetic ganglia, adrenal medulla, and other sites.
• So, The patterns of distribution of these cells correlates with the sites of primary neuroblastoma presentation.
• it may be found from orbit to pelvis where sympathetic nervous tissue is found.

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EPIDEMIOLOGY

• It is the most common solid tumour of infancy and childhood. Incidence decreases every consecutive year up to age 10 years, after which the disease is rare
• It occurs in l in I 0,000 live births.
• Incidence of neuroblastoma is higher in white children than in black children. However, race does not appear to have any effect on outcome.
• male-to-female ratio of 1.2:1.

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AETIOLOGY/RISK FACTORS

• The cause of neuroblastoma is unknown, and no specific environmental exposure or risk factors have been identified.
• Factors investigated for which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol or tobacco use, and paternal occupational exposures.
• Neuroblastoma has been known to occur in the setting of other disorders that are linked to abnormal development of neural crest tissues, such as Hirschsprung disease or central congenital hypoventilation syndrome.
• It can occur anywhere in sympathetic chain but most common in adrenal gland (40%).
• As the name suggests, the tumour occurs due to malignant proliferation of the neuroblasts or failure of maturation of primitive sympathetic nerve cells, the neuroblasts.

TYPES

1. Pepper type is right side adrenal neuroblastoma with liver secondaries. Common in infants.

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2. Hutchinson’s type is left side adrenal neuroblastoma with secondaries in orbit and skull. Common in late childhood. Secondaries in the skull mimics specular osteogenic sarcomas.

CLINICAL FEATURES

• 50% of children present to the hospital under the age of one year and 80-90% are less than 3 years of age.
• Signs and symptoms of neuroblastoma vary with site of presentation. 
• Generally, An abdominal mass is the most common presenting feature which include abdominal pain, emesis, weight loss, anorexia, fatigue, and bone pain. 
• The abdominal mass has all the features of a renal mass but location is slightly higher. It is firm to hard, not moving with respiration, nodular and fixed(non mobile), crosses the midline.
• Functional tumours produce diarrhoea and hypokalaemia due to release of vasoactive intestinal polypeptide (VIP), sweating and flushing due to release of catecholamines.

• The child is sick with weight loss, fever, abdominal distension, anaemia, etc.
• Approximately 2% of patients present with Dancing eye syndrome and opsomyoclonus (characterized by the presence of myoclonic jerking and random eye movements).
• Raccoon's eye sign is infraorbital ecchymosis due to secondaries in retro-orbital region.
• Proptosis and periorbital swellings are due to bony metastasis and subcutaneous nodules are quite common
• Posterior mediastinal neuroblastomas can produce cord compression and even paraplegia due to protrusion within the spinal canal (dumbbell tumours).
• Hypertension, fever, weight loss, anaemia, flushing (due to catecholamine release) and sweating.

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DIFFERENTIAL DIAGNOSES�

• Wilms Tumor which is mobile, with smooth surface, moves with respiration, does not cross the midline.
• Pediatric Rhabdomyosarcoma

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INVESTIGATIONS

• Any child with a presumed diagnosis of neuroblastoma or any other childhood cancer should be referred to a pediatric cancer center for proper care and evaluation. Laboratory studies should include the following:
• CBC count and differential (Anemia or other cytopenias suggest bone marrow involvement.)
• Vanillyl mandelic acid (VMA) and homovanillic acid (HVA) are the byproducts of catecholamines passed in the urine. 24-hour urinary excretion of catecholamines and these two metabolites will be very high.
• Serum creatinine
• Liver function tests

• Electrolytes panel
• U/S, CT to assess the mass and secondaries in liver. MRI is better than CT.
• Plain X-ray abdomen shows stippled calcification. X-ray chest is done to rule out cannon-ball secondaries.
• Bone marrow biopsy may be positive in 60% cases.

MEDICAL CARE�

• Care of children with neuroblastoma is provided by a multidisciplinary team involving pediatric oncology, radiation oncologists, surgeons, and anesthesiologists, as well as nurse practitioners, nurses, pharmacists, psychologists, and physical and occupational therapists dedicated to the special needs of these children.

TREATMENT

• Intermediate and high risk cases can be managed by chemotherapy followed by surgery.
• Early cases respond very well to surgical excision. Adrenalectomy (Complete surgical excision).
• Post surgical radiotherapy and folic acid supplements are useful.

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• Low risk groups are treated by surgery. Intermediate risk groups are treated by surgery and multidrug chemotherapy. High risk groups are treated by high dose multidrug chemotherapy and later surgery.

PROGNOSIS

• A patient with low-stage disease generally has a good prognosis, and patients usually receive standard chemotherapy, surgery, and/or radiation as necessary.
• Patients with disseminated disease at presentation have a high recurrence rate and a poor outcome.

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FOLLOW UP

• Patients are periodically monitored in the clinic after each course of therapy to monitor for complications and to assess response to therapy with diagnostic imaging.
• Follow-up care includes monitoring of urinary catecholamines, physical examination, and diagnostic imaging.
• Patients who remain free of recurrent disease for 5 years are considered cured.

COMPLICATIONS

• Cord compression from a para-spinal tumor. 
• severe hypertension
• Renal insufficiency
• After several cycles of therapy patients may develop impaired renal function, hearing loss.