Teaching Case

A premature female infant born at 31-weeks gestational age, was admitted to hospital for investigation of hepatomegaly at the age of 3-weeks. A blue-coloured subcutaneous nodule had been noted on her left leg at the time of admission.

A female infant was delivered by emergency caesarean section at 31-weeks gestational age, following suspected placental abruption. At 3-weeks of age her mother noted abdominal distension and she was brought to the Emergency Department. Clinical examination revealed hepatomegaly and a blue-coloured subcutaneous nodule on her left leg. Over the following 24 hours, more than 20 similar subcutaneous nodules developed over the baby’s trunk and limbs. An ultrasound scan of the abdomen revealed a right-sided adrenal mass lesion and confirmed massive hepatomegaly, the liver having an heterogeneous echotexture. Appearances were thought to represent neuroblastoma with hepatic metastases. The subcutaneous nodules raised the possibility of stage IVs disease. The infant was transferred to the oncology unit for further management. The ultrasound findings were confirmed on a CT scan of the abdomen. Both MIBG and isotope bone scans were negative for bone involvement. Over the next few days the baby developed respiratory distress, due to the enlarged liver causing diaphragmatic splinting. Histological diagnosis of neuroblastoma was confirmed and the infant commenced on appropriate chemotherapy. Her abdominal distension reduced and she was weaned from the ventilator.

Neuroblastomas are tumours of the primitive neural crest cells, which may arise anywhere in the sympathetic ganglion chain or the adrenal medulla. Stage IVs disease (‘s’ for special) is a variant of neuroblastoma that occurs in infants less than 12-months of age. It represents only 4% of neuroblastoma cases. Patients characteristically present in the neonatal period or soon afterwards, with abdominal distension secondary to hepatomegaly or with blue-coloured subcutaneous nodules; the latter has been referred to as a “blueberry muffin”. Respiratory embarrassment can occur due to massive hepatomegaly. Stage IVs disease spreads to the liver and subcutaneous tissues. It may also be found in the bone marrow, but not the trabecular bone. The primary adrenal tumour mass may be uni- or bilateral and is usually small. Ultrasound easily demonstrates the hepatic abnormality and the adrenal mass. CT or MR are required for formal staging, alongside an isotope bone scan to exclude bone metastases. Whilst chemotherapy or low dose radiotherapy may be required acutely for those infants with respiratory difficulties, spontaneous regression of the tumour is recognised in some children. The 5-year-survival rate for infants with stage IVs neuroblastoma is over 80%, which compares favourably to stage IV disease, where the prognosis remains dismal at less than 15% survival. However, the presence of MCYN gene amplification in stage IVs neuroblastoma patients carries a worse prognosis.