Paediatrics: Neuroblastoma

Neuroblastoma

A malignant embryonal tumour derived from neural crest tissue with a wide spectrum of behaviour. It represents 7% of all childhood malignan-cies. Median age of presentation at 2yrs. Sites of involvement include:

·  the adrenal glands (32%);

·  the sympathetic chain:

·  abdomen (28%);

·  thorax (15%);

·  pelvis (6%);

·  neck (2%).

May be locally invasive; surrounds, rather than displaces vessels and other structures. Distant metastases to bone, bone marrow, liver, CNS, lungs, and skin (especially infants).

Presentation

Non-specific and variable. Depends on site, spread, and metabolic effects:

·  Palpable mass (may be painless).

·  Compression of nerves (e.g. Horner’s, spinal cord), airway, veins, bowel.

·  Bone: pain and/or limp.

·  Lymphadenopathy and signs of pancytopenia.

·  Sweating, pallor, watery diarrhoea, and hypertension.

Specific diagnostic tests

·  Urine catecholamine (VMA or homovanillic acid (HVA)) to creatinine ratio, which is raised in >80% cases.

·  ¹³¹I-MIBG uptake scan: usually +ve.

Treatment

·  Biological factors, such as MYCN amplification and 17q gain, strongly influence prognosis and treatment.

·  Completely resected localized neuroblastoma may need no further treatment.

·  Incompletely resected, stage 3 tumours require chemotherapy and possibly adjuvant radiotherapy.

·  Stage 4 (disseminated) and MYCN +ve stage 3 tumours require induction chemotherapy, surgery, high dose chemotherapy with autologous stem cell rescue, radiotherapy and differentiation therapy with cis-retinoic acid. Targeted antibody treatment is increasingly employed as part of the approach to treatment in the context of clinical trials.

·  Exception: young (<18 mths old) stage 4 patients with favorable biological features receive moderately intensive chemotherapy and surgery only.

Prognosis

Disseminated neuroblastoma only cured in 20–30%, despite intensive treatment. Survival in low risk cases (low stage, infants) is >90%.

Poor prognostic factors in neuroblastoma

·  Age >18mths.

·  Stage 3 and 4 disease.

·  Raised serum ferritin.

·  Raised LDH.

·  Raised neuron-specific enolase (NSE).

·  Unfavourable histology.

·  MYCN oncogene amplification.

·  17q gain/1p loss.

Relapse treatment

Options include further surgery, chemotherapy, and/or radiotherapy, depending on p treatment. After previous high dose chemotherapy and stem cell transplant, cure is unrealistic. Treatment aimed at palliation.

Infant neuroblastoma (stage IVs)

Disseminated disease restricted to bone marrow, liver, and skin. Characteristically resolves spontaneously. Chemotherapy is only for life-threatening symptoms. Resection (complete or partial) is usually sufficient for localized disease.