Neuroblastoma
Tumor Behavior
Proliferation and Invasion:
Neuroblastoma cells proliferate uncontrollably, invade local tissues, and metastasize to distant sites such as the bone marrow, liver, and skin.
Catecholamine Secretion:
Tumor cells may produce catecholamines (dopamine, norepinephrine), leading to elevated levels of their metabolites (e.g., vanillylmandelic acid [VMA] and homovanillic acid [HVA]) in urine or blood.
Immune Evasion:
Tumor cells employ mechanisms to evade immune surveillance, such as downregulating major histocompatibility complex (MHC) molecules.
Anatomical Structures Involved
Local Tumor Effects
Adrenal Mass: Compression of adjacent abdominal organs (e.g., kidneys, intestines) may cause symptoms like abdominal pain, constipation, or urinary retention.
Thoracic Tumors: May compress the trachea, causing breathing difficulties.
Cervical Tumors: Can present with Horner's syndrome (ptosis, miosis, and anhidrosis) due to sympathetic chain involvement.
Metastatic Spread
Bone marrow: Causes anemia and thrombocytopenia.
Bones: Leads to pain, fractures, or skull deformities.
Liver: May result in hepatomegaly.
Skin: Causes bluish subcutaneous nodules (especially in infants with Stage 4S).
Lymph Nodes: Particularly regional lymph nodes.
Metastasis
Distant Spread:
Bone marrow: Results in anemia, thrombocytopenia, and fatigue.
Bones: Leads to bone pain and fractures.
Liver: Causes hepatomegaly.
Skin: Results in bluish nodules (often seen in infants with Stage 4S disease).
Unique Features in Infants (Stage 4S or MS)
Tumors in infants under 18 months can spontaneously regress due to immune factors or differentiation of neuroblastoma cells into benign ganglioneuroma.
Genetic and Molecular Mechanisms
MYCN Amplification:
MYCN is an oncogene whose amplification leads to unchecked cell proliferation, reduced apoptosis, and aggressive tumor behavior.
Found in approximately 20-25% of neuroblastoma cases and is a poor prognostic factor.
ALK Gene Mutations:
Mutations in the ALK (Anaplastic Lymphoma Kinase) gene are associated with both familial and sporadic neuroblastoma.
Chromosomal Abnormalities:
Deletions on chromosomes 1p and 11q are associated with tumorigenesis.
Gain of chromosome 17q is common and linked to worse outcomes.
Loss of Differentiation:
Tumor cells retain characteristics of immature neural crest cells, with incomplete differentiation into normal sympathetic nervous tissue.
Common Sites of Origin
Adrenal Glands (40-50%)
Sympathetic Ganglia (Anywhere Along the Sympathetic Chain)
Abdomen (25-30%): Besides the adrenal glands, tumors can develop in retroperitoneal sympathetic ganglia.
Thorax (15-20%): Includes sympathetic ganglia in the chest.
Cervical Region (5%): Rarely occurs in the neck but can affect cervical sympathetic ganglia.
Pelvis (Rare): Tumors in the pelvic sympathetic chain are uncommon.
Prognosis
Dependent on age at diagnosis, tumor biology (e.g., MYCN gene amplification), and stage. Younger children often have better outcomes.
Origin
Neural Crest Cells: Neuroblastoma arises from undifferentiated or poorly differentiated neural crest cells.
These cells normally differentiate into components of the sympathetic nervous system (e.g., adrenal medulla and sympathetic ganglia).
Failure of these cells to mature properly can result in tumor formation.
Common Sites:
Adrenal glands (most frequent primary site).
Sympathetic ganglia in the abdomen, chest, neck, or pelvis.
Symptoms
Depending on tumor location, symptoms can include abdominal swelling, pain, loss of appetite, weight loss, or specific neurological symptoms if the tumor affects the spinal cord.
Risk Factors
Genetic Factors
Family History
Gene Mutations:
MYCN Amplification:
Age
Neuroblastoma is most common in children under the age of 5 years.
It is rarely diagnosed in adolescents or adults.
Congenital Syndromes
Beckwith-Wiedemann syndrome
Hirschsprung disease
Neurofibromatosis type 1 (NF1)
Environmental Factors
Prenatal exposures to toxins, pesticides, or other harmful substances have been hypothesized as potential risks.
Developmental Factors
Neuroblastoma originates from embryonic neural crest cells, and abnormal development or differentiation of these cells during fetal development can lead to cancer.
Parental Factors
Advanced parental age or exposure to certain chemicals or medications before conception or during pregnancy has been studied but lacks definitive evidence.
Ethnicity
Neuroblastoma is slightly more common in children of white ethnicity compared to other ethnic groups.
Sex
Boys are slightly more likely to develop neuroblastoma than girls, though the difference is not significant.
Diagnosis
Imaging
MRI
CT- Scans
Metaiodobenzylguanidine
Biopsy
Pathological Confirmation.
Blood/Urine Tests
Elevated catecholamines (e.g., vanillylmandelic acid and homovanillic acid).
Staging
Typically staged from localized (Stage 1) to widely spread (Stage 4 or 4S, the latter unique to infants under 1 year).
Treatment
Varies by stage and risk group, often involving:
Surgery
Chemotherapy
Radiation therapy
Stem cell transplant
Immunotherapy (e.g., anti-GD2 monoclonal antibodies)