• Clinical science

Neuroblastoma

Summary

Neuroblastoma is a malignant neuroendocrine tumor of the sympathetic nervous system that originates from neural crest cells. It is the most common extracranial solid malignancy in children and the most common malignancy found in infants. Given its origin, neuroblastoma can occur in any aggregation of sympathetic nervous tissue, including the adrenal glands, the sympathetic chain, and the paraganglia (e.g., the carotid body). The clinical presentation is mainly determined by the site of the primary tumor, if it secretes catecholamines, and whether it has metastasized. In most cases, neuroblastomas stem from the adrenal glands within the abdominal cavity and present as a palpable abdominal mass that can cross the midline. Urine tests for catecholamine metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) play an important role in diagnosis. Treatment is determined mainly by patient age at the time of diagnosis, clinical stage, and possible amplification of the MYCN oncogene. The prognosis depends on disease progression and is very good in early stages. Spontaneous remission may occur even in cases of metastatic disease.

Definition

Neuroblastoma is a malignant, embryonal neuroendocrine neoplasm of the sympathetic nervous system that originates from neural crest cells; , potentially secretes catecholamines; , and is usually found in the adrenal glands or sympathetic ganglia.
References:[1]

Epidemiology

References:[2][3][4][5]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3]

Clinical features

General symptoms

Localized symptoms

Location Associated symptoms

Abdomen (in > 60% of cases)

  • Palpable, firm, irregular abdominal mass that may cross the midline (in contrast to Wilms tumor, which is smooth and usually does not cross the midline)
  • Abdominal distension and pain
  • Hepatomegaly
  • Constipation

Chest (in ∼ 20% of cases): particularly paravertebral ganglia

Neck

Orbit of the eye

Bones

Skin

  • Subcutaneous nodules

Paraneoplastic syndromes

References:[7][8][9][10][11][12]

Stages

International Neuroblastoma Staging System (INSS) [13]
Stage Definition
1
  • Localized tumor
  • Complete gross excision with or without microscopic residuals
  • Negative ipsilateral lymph nodes
2A
2B
  • Localized tumor
  • Complete or incomplete gross excision
  • Positive ipsilateral lymph nodes
3
4
  • Any tumor with dissemination to distant lymph nodes or other organs (e.g., bone, liver, skin), with the exception of Stage 4S disease
4S

Diagnostics

Laboratory tests

Other procedures

References:[7]

Pathology

  • Homer Wright rosettes: Halo-like clusters of neuroblast cells surrounding a central pale area containing neuropil (associated with tumors of neuronal origin such as neuroblastoma, medulloblastoma, primitive neuroectodermal tumors, and pineoblastoma)
  • Small round blue cells with hyperchromatic nuclei
  • Bombesin and NSE positive

References:[3][14][15]

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Neuroblastoma patients are treated based on their risk category (low, intermediate, or high), which is based on the stage of their neuroblastoma (extent of disease), age at diagnosis, and the presence/absence of MYCN amplification.

  • Low risk: generally children with early-stage disease (Stages 1–2) and no MYCN amplification
  • Intermediate risk: generally children with intermediate and late-stage disease (Stages 3–4) and no MYCN amplification
  • High risk: generally children with late-stage disease and/or MYCN amplification
  • Stage 4S (an exception): disseminated disease in infants (< 12 months)
    • Better prognosis than other stage 4 neuroblastoma and spontaneous regression is very common
    • Children with Stage 4S belong to the low-risk or intermediate-risk groups unless they have a MYCN amplification, in which case they are high-risk patients
Treatment of neuroblastoma
Treatment Low-risk neuroblastoma Intermediate-risk neuroblastoma High-risk neuroblastoma
Observation only X
Preoperative chemotherapy (e.g., doxorubicin, cyclophosphamide, etoposide, and a platinum drug) X X X
Surgery X X X
Postoperative chemotherapy X X
Radiation X X
GD2 antibody, dinutuximab, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 2 (IL-2), and cis-retinoic acid X
Other postoperative therapies (e.g., MIBG therapy) X

Spinal cord compression requires immediate surgical decompression or chemotherapy to shrink tumor tissue!

References:[16][17][18][19][20]

Prognosis

  • Prognosis depends on the risk group. Important factors include:
    • Age
    • Children with MYCN amplification are classified as high risk
    • Histopathology, disease dissemination and biochemical markers

References:[19][21]