Neuroblastoma

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Age-Related Anatomy topic

Older Children: Neuroblastoma may present with fewer localized symptoms due to more space within body compartments.

Infants: Smaller thoracic and abdominal cavities mean tumors may compress nearby organs more easily.

4. Catecholamine Production

Neuroblastoma cells may produce excess epinephrine, norepinephrine, or their metabolites, leading to systemic symptoms (e.g., hypertension, flushing, sweating).

Sympathetic Nervous System Anatomy

Adrenal Medulla: Acts as a modified sympathetic ganglion, making it a common site for neuroblastoma.

Prevertebral Ganglia: Found in the abdominal region near major blood vessels (e.g., celiac ganglion).

Sympathetic Chain: Runs parallel to the vertebral column and includes the paravertebral ganglia, which are frequent sites of neuroblastoma development.

Neuroblastoma

Treatment

Varies by stage and risk group, often involving:

Immunotherapy (e.g., anti-GD2 monoclonal antibodies)

Stem cell transplant

Radiation therapy

Chemotherapy

Surgery

Staging

Typically staged from localized (Stage 1) to widely spread (Stage 4 or 4S, the latter unique to infants under 1 year).

Diagnosis

Blood/Urine Tests

Elevated catecholamines (e.g., vanillylmandelic acid and homovanillic acid).

Biopsy

Pathological Confirmation.

Imaging

Metaiodobenzylguanidine

CT- Scans

MRI

Risk Factors

Sex

Boys are slightly more likely to develop neuroblastoma than girls, though the difference is not significant.

Ethnicity

Neuroblastoma is slightly more common in children of white ethnicity compared to other ethnic groups.

Parental Factors

Advanced parental age or exposure to certain chemicals or medications before conception or during pregnancy has been studied but lacks definitive evidence.

Developmental Factors

Neuroblastoma originates from embryonic neural crest cells, and abnormal development or differentiation of these cells during fetal development can lead to cancer.

Environmental Factors

Prenatal exposures to toxins, pesticides, or other harmful substances have been hypothesized as potential risks.

Congenital Syndromes

Neurofibromatosis type 1 (NF1)

Hirschsprung disease

Beckwith-Wiedemann syndrome

Age

It is rarely diagnosed in adolescents or adults.

Neuroblastoma is most common in children under the age of 5 years.

Genetic Factors

Gene Mutations:

Family History

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.

Origin

Common Sites:

Sympathetic ganglia in the abdomen, chest, neck, or pelvis.

Adrenal glands (most frequent primary site).

Neural Crest Cells: Neuroblastoma arises from undifferentiated or poorly differentiated neural crest cells.

Failure of these cells to mature properly can result in tumor formation.

These cells normally differentiate into components of the sympathetic nervous system (e.g., adrenal medulla and sympathetic ganglia).

Prognosis

Dependent on age at diagnosis, tumor biology (e.g., MYCN gene amplification), and stage. Younger children often have better outcomes.

Common Sites of Origin

Sympathetic Ganglia (Anywhere Along the Sympathetic Chain)

Pelvis (Rare): Tumors in the pelvic sympathetic chain are uncommon.

Cervical Region (5%): Rarely occurs in the neck but can affect cervical sympathetic ganglia.

Thorax (15-20%): Includes sympathetic ganglia in the chest.

Abdomen (25-30%): Besides the adrenal glands, tumors can develop in retroperitoneal sympathetic ganglia.

Adrenal Glands (40-50%)

Genetic and Molecular Mechanisms

Loss of Differentiation:

Tumor cells retain characteristics of immature neural crest cells, with incomplete differentiation into normal sympathetic nervous tissue.

Chromosomal Abnormalities:

Gain of chromosome 17q is common and linked to worse outcomes.

Deletions on chromosomes 1p and 11q are associated with tumorigenesis.

ALK Gene Mutations:

Mutations in the ALK (Anaplastic Lymphoma Kinase) gene are associated with both familial and sporadic neuroblastoma.

MYCN Amplification:

Found in approximately 20-25% of neuroblastoma cases and is a poor prognostic factor.

MYCN is an oncogene whose amplification leads to unchecked cell proliferation, reduced apoptosis, and aggressive tumor behavior.

Metastasis

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.

Distant Spread:

Skin: Results in bluish nodules (often seen in infants with Stage 4S disease).

Liver: Causes hepatomegaly.

Bones: Leads to bone pain and fractures.

Bone marrow: Results in anemia, thrombocytopenia, and fatigue.

Anatomical Structures Involved

Lymph Nodes: Particularly regional lymph nodes.

Skin: Causes bluish subcutaneous nodules (especially in infants with Stage 4S).

Liver: May result in hepatomegaly.

Metastatic Spread

Bones: Leads to pain, fractures, or skull deformities.

Bone marrow: Causes anemia and thrombocytopenia.

Local Tumor Effects

Cervical Tumors: Can present with Horner's syndrome (ptosis, miosis, and anhidrosis) due to sympathetic chain involvement.

Thoracic Tumors: May compress the trachea, causing breathing difficulties.

Adrenal Mass: Compression of adjacent abdominal organs (e.g., kidneys, intestines) may cause symptoms like abdominal pain, constipation, or urinary retention.

Tumor Behavior

Immune Evasion:

Tumor cells employ mechanisms to evade immune surveillance, such as downregulating major histocompatibility complex (MHC) molecules.

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.

Proliferation and Invasion:

Neuroblastoma cells proliferate uncontrollably, invade local tissues, and metastasize to distant sites such as the bone marrow, liver, and skin.