Neuroblastoma: Case

Framing the case

This two-year-old girl has the classic presentation of a metastatic neuroblastoma. The firm, irregular abdominal mass that crosses the midline, the irritability and the fever, the periorbital ecchymosis of the orbital metastasis, and the mild hypertension of the catecholamine secretion together make the diagnosis, and the framework that organises the case is the International Neuroblastoma Risk Group staging system and the risk stratification by the MYCN amplification. The first priority is the confirmation of the catecholamine secretion and the staging of the disease extent. [1][2]

Confirming the diagnosis

The urinary catecholamine metabolites are the first-line confirmation, and the measurement of the vanillylmandelic acid and the homovanillic acid in a random urine sample, corrected for the creatinine, confirms the diagnosis in over ninety percent of neuroblastomas. The ultrasound confirms the abdominal mass and its origin from the adrenal gland rather than the kidney, and the contrast-enhanced magnetic resonance imaging defines the anatomy, the extension across the midline and the image-defined risk factors. The iodine-123 metaiodobenzylguanidine scan is the functional imaging that maps the disease extent, and the MIBG scan is positive in over ninety percent of neuroblastomas. [1][4]

Staging and risk stratification

The staging follows the International Neuroblastoma Risk Group system. The magnetic resonance imaging shows the large right adrenal mass extending across the midline and encasing the aorta and the inferior vena cava, which are the image-defined risk factors that assign the L2 stage. The iodine-123 MIBG scan shows the uptake in the primary mass, the orbital metastasis and the bone marrow, which assigns the M stage for the distant metastatic disease. The bone marrow aspirate and trephine biopsy confirm the marrow involvement with the clumps of the small round blue cells. The percutaneous core biopsy of the primary tumour is sent for the histology and the molecular analysis, and the fluorescence in situ hybridisation shows the MYCN amplification with more than ten copies of the gene per cell. [2][5]

The definitive management

This child is in the high-risk group, because she is over eighteen months with the metastatic disease and the MYCN amplification, and the treatment runs through the full sequence of the intensive multimodal therapy. The induction chemotherapy uses the combination of the cisplatin, the etoposide, the cyclophosphamide, the vincristine and the doxorubicin over approximately four months, and the interim assessment of the response guides the timing of the surgery. The surgical resection of the primary tumour is performed after the induction, aiming for the gross total resection. The myeloablative consolidation with the autologous stem cell rescue, followed by the external beam radiotherapy to the primary site, delivers the tumoricidal dose that the conventional chemotherapy cannot. The anti-GD2 immunotherapy with the dinutuximab beta, in combination with the interleukin-2 and the isotretinoin, completes the consolidation and targets the minimal residual disease. [1][12]

Contrasting the opsoclonus-myoclonus-ataxia syndrome

The examiner asks the candidate to contrast this high-risk neuroblastoma with the child who presents with the opsoclonus, the myoclonus and the ataxia. A child with the opsoclonus-myoclonus-ataxia syndrome has neuroblastoma until proven otherwise, and the search for the occult tumour, with the urinary catecholamines, the iodine-123 MIBG scan and the magnetic resonance imaging, is mandatory. The neuroblastoma associated with the syndrome is typically the low-stage, favourable-biology tumour, and the tumour itself carries an excellent prognosis with the surgical resection. The devastating contrast is the neurological outcome, because the autoimmune injury persists and causes the cognitive, behavioural and motor sequelae that may last for life, even when the tumour is cured. The management of the neurological syndrome uses the immunomodulation with the corticosteroids, the intravenous immunoglobulin and the rituximab. [6][9]

Communication and the family

The family is counselled honestly and with the realistic information about the risk-group-specific prognosis. The candidate names the diagnosis, explains that the high-risk neuroblastoma carries a five-year survival below fifty percent despite the most intensive treatment in the paediatric oncology, and that the treatment runs through the induction, the surgery, the myeloablative consolidation, the radiotherapy and the immunotherapy over approximately eighteen months. The parents are introduced to the multidisciplinary team, given a written plan, taught the fever and the neutropenia emergencies, and supported by the social work and the educational liaison. The survivorship surveillance is begun from the diagnosis, with the watch for the hearing loss, the cardiotoxicity, the endocrine disturbances and the second malignancy. The fellow who holds the science and the humanity together in this conversation demonstrates the reasoning the boards reward. [1][12]