Neuroblastoma C47.-; C72.2-; C72.5; C47.0; C69.6; C47.1; C47.2; C47.3; C47.4; C47.5; C47.6; C47.8; C48.-; C48.0; C74.-; C74.1;

Malignant tumor of the sympathetic nervous system and after CNS tumors the most common malignant solid tumor in childhood (Schulte JH et al. 2015). 8-10% of all malignant childhood processes involve neuroblastoma (Ahmed AA et al. 2017). The malignant tumour is derived from the cells of the neural crest. The tumour can occur in all tissues in which there are accumulations of sympathetic nerve cells, such as in the adrenal medulla, in the sympathetic trunk, the paravertral border strand that extends from the neck to the coccyx, or in the paraganglia.

The clinical symptoms are significantly influenced by the location of the tumours, and also by the very different growth behaviour between spontaneous regression of the initial tumour and the tendency to metastasise.

Clinical stages according to Evans:

• Stage 1: tumour limited to the organ of origin
• Stage 2a: Infiltration of the environment without crossing the midline without lymph node involvement
• Stage 2b: Infiltration of the environment without crossing the midline with ipsilateral lymph node involvement
• Stage 3: Crossing the centre line
• Stage 4: Metastasis in other organs and distant lymph nodes
• Stage 4S: Localised primary tumour in infants in the first year of life, which metastasises to the skin, liver and/or bone marrow, but not to the bones (prognosis better than stage 4); spontaneous regression is not uncommon

After CNS tumours, most common malignant solid tumour in childhood.

Unclear; possible cause is an amplification of the oncogene N-myc (MYCN amplification) with deletion of the short arm of chromosome 1 (1p deletion). Since neuroblastoma-specific genetic alterations have not been described, it is assumed that the disease is heterogeneous.

Mean age of the disease: 2.0 years, also younger. In 50% of the affected persons stage 4 is present at the time of diagnosis

Different symptoms depending on the location of the tumor.

Localizations and clinic:

• Abdominal tumor (>60%): Abdominal pain, failure to thrive/weight loss, vomiting/appetence. Symptomatology due to increased catecholamine production, e.g. hypertension or chronic diarrhea. Continued fever.
• Head/face/neck tumor: Horner's syndrome; retrobulbar neuroblastoma: evidence of eyelid kchymosis (raccoon eyes = spectacled hematomas); heterochromia of the iris and skin pallor after impact or blow to a metastasis with blue-green intrinsic color due to catecholamine release are special characteristics. ,
• Thoracic tumor (about 20%): Cough, dyspnea, stridor, possible paraplegic symptoms in hourglass tumors.
• Bone marrow tumor: bone pain

Histological classification of malignancy grades according to Hughes:

• Grade 1: Mix of undifferentiated cells and mature ganglion cells
• Grade 2: Immature cells together with some maturing ganglion cells
• Grade 3: Undifferentiated cells, occasional rosette formation

Urine: catecholamine degradation products (especially vanillin mandelic acid, homovanillic acid) increased in 24-h collecting urine; blood: catecholamine degradation products increased; also LDH, ferritin and the neuron-specific enolase (NSE).

X-ray thorax: CT or MRT to exclude an hourglass tumour

Sono abdomen; MIBG scintigraphy; bone marrow puncture to exclude bone marrow infiltration

Nephroblastoma; leukemic infiltrates; neoplasms from the neuroectodermal tumor Ewing sarcoma family, neuroendocrine tumors.

Depending on the age of the child and stage of the disease: In case of localized tumor and lack of MYCN amplification: Waiting behaviour: spontaneous regression is possible (Whittle SB et al. 2017). For "high-risk neuroblastoma" (HR-NB) high-dose chemotherapy, tumor resection and/or radiotherapy are used. In case of hourglass tumors immediate surgery is indicated due to the risk of paraplegia! Immunotherapies are in clinical trials, for example with monoclonal GD2 antibodies (Sait S et al. 2017).

The lower the tumor stage at the time of treatment, the better the prognosis:

• Stage 1 and 2 (>90% cure rate)
• Stage 3 and 4S (approx. 60-70% cure rate)
• Stage 4 (10-20% chance of survival)

The older the child at tumour detection, the worse the prognosis. Even with metastases, spontaneous regression is possible in the first 15 months of life (Ahmed AA et al. 2017). A high LDH is associated with a poor prognosis. Only at an advanced stage do symptoms such as reduced physical performance, exercise dyspnoea (breathing difficulties under stress) or peripheral oedema (Ayerza disease) appear.

1. Ahmed AA et al (2017) Neuroblastoma in children:Update on clinicopathologic and genetic prognostic factors. Pediatrics Hematol Oncol 34:165-185.
2. Sait S et al (2017) Anti-GD2 immunotherapy for neuroblastoma. Expert Rev Anticancer Ther 17:889-904.
3. Schulte JH et al (2015) Neuroblastoma. Crit Rev Oncog 20(3-4):245-70.https://www.ncbi.nlm.nih.gov/pubmed/26349419
4. Whittle SB et al (2017) Overview and recent advances in the treatment of neuroblastoma. Expert Rev Anticancer Ther. 17:369-386.