Neuroblastoma in children

Clinical presentation and associated syndromes

Early symptoms of neuroblastoma are often related to metastasis: bone pain, exophthalmos due to orbital lesions, anemia, fever, and weight loss. The tumor frequently manifests with specific syndromes:

• Horner's syndrome: occurs when the stellate ganglion is affected (cervical or thoracic localization).
• Hormonal activity: catecholamine excess causes arterial hypertension, and the secretion of vasoactive intestinal peptide (VIP) causes intractable watery diarrhea.
• Paraneoplastic syndrome: opsoclonus-myoclonus ataxia syndrome of infancy (pathogenesis unknown).
• Dumbbell syndrome (dumb-bell syndrome): extradural extension leading to spinal cord compression.

In children under 1 year of age, the disease is often accompanied by extensive liver and bone marrow metastases. Despite this, the prognosis is usually favorable due to the tumor's tendency toward spontaneous regression. The diagnosis is confirmed by finding neuroblastoblasts in a bone marrow aspirate combined with elevated levels of catecholamine metabolites. In the differential diagnosis, it is important to remember ganglioneuromas—benign posterior mediastinal masses found in older children (average around 7 years).

Diagnostic imaging: ultrasound, CT, and MRI

The imaging algorithm depends on the localization and the patient's age.

1. Radiography: may show a calcified mass, erosion of the pedicles of the vertebrae in case of intraspinal growth, or a "moth-eaten" destruction of the metaphyses of long tubular bones.
2. Ultrasonography (US): the primary screening method for newborns. The ultrasound picture is variable (cystic, solid, or heterogeneous) and may resemble adrenal hemorrhage. Features favoring a tumor include increased size, the appearance of internal echoes, and abundant vascularity on color Doppler.
3. Computed tomography (CT): requires bolus contrast enhancement. Shows a large heterogeneous mass. In 85% of cases, calcifications are detected, and low-density areas correspond to zones of necrosis or hemorrhage.
4. Magnetic resonance imaging (MRI): strictly indicated for paraspinal masses to assess extradural extension. On T1- and T2-weighted images, the tumor produces elongated signals; high intensity on T1 indicates hemorrhage. MRI is also superior to CT in detecting bone marrow involvement.

Radionuclide imaging

$^{123}$I-metaiodobenzylguanidine ($^{123}$I-mIBG) scintigraphy plays a key role. The radiopharmaceutical is a norepinephrine analogue and is taken up with high specificity by cells of the sympathetic nervous system. This allows for locating the primary focus and assessing metastasis. The method is indispensable for differentiating fibrosis from viable residual tumor after chemotherapy. Since mIBG does not reliably distinguish between bone marrow uptake and cortical bone involvement, all patients must undergo $^{99m}$Tc-MDP bone scintigraphy (bone metastases are present in 2/3 of patients at diagnosis).

Staging: INSS and INRGSS

For many years, the INSS system was used, which was based on the extent of surgical resection and lymph node biopsy. This created problems: the stage depended on the surgeon's subjective assessment, and infants with localized disease (who were only observed) could not be adequately staged.

The modern INRGSS system eliminates this drawback. It is based on diagnostic imaging and the identification of risk factors—IDRFs (Image-Defined Risk Factors). The purpose of IDRFs is to determine whether the tumor can be safely resected. Strict criteria are used to describe the relationship of the tumor to adjacent structures:

• Separation — presence of a tissue plane.
• Contact — no tissue plane, but no invasion.
• Encasement — vessel is surrounded by masses for more than 50% of its circumference.
• Compression — reduction of the short axis of the airways.

Class and exam questions

What else to study on this topic

• Imaging features of ganglioneuromas and ganglioneuroblastomas.
• Detailed analysis of IDRF risk factors based on CT and MRI data.
• Specifics of stage 4s (MS) in infants in their first year of life.
• Use of 18F-FDG PET/CT and whole-body MRI (WBMRI) in pediatric oncology.
• Pathogenesis of opsoclonus-myoclonus ataxia syndrome in neuroblastoma.

Other Topics in "Pediatric Diagnostic Radiology"

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