A Rare Clinical Presentation of Neuroblastoma: A Boy’s Respiratory Distress and Neck Swelling
A boy aged 2 years and 9 months was admitted to a hospital’s pediatric unit with a chief concern of difficulty breathing, which had started a few weeks ago. At that time, his primary care provider had treated him for a presumed upper respiratory infection and had prescribed an unknown antibiotic.
The boy was seen by his primary care provider again 4 days prior to admission and was given an albuterol sulfate inhaler and a corticosteroid course, with no improvement. Two nights prior to admission, he was seen in the emergency department (ED) and was started on amoxicillin, fluticasone nasal spray, and albuterol nebulizer treatments every 4 hours.
On the night of admission, the patient had developed deep subcostal and sternal retractions while sleeping, and he was brought back to the ED. On further review of the boy’s symptoms, the parents denied any fever, cough, congestion, vomiting, abdominal pain, or other symptoms. He had been eating and drinking well, but recently had started to prefer only soft foods. He had no significant past medical history or surgical history. His developmental was normal, and he had no known sick contacts and no recent travel.
In the ED, his vital signs initially were stable, and he was afebrile. He then began to have intermittent oxygen desaturations into the upper 80 percent range, lasting a few seconds, and resolving with repositioning.
On physical examination, he generally looked tired but was not lethargic. He was in moderate respiratory distress with sternal and subcostal retractions and inspiratory and expiratory stridor at rest. Lung fields were clear with no wheezing or rales. He had left nasal turbinate hypertrophy; a left tonsil with 4+ hypertrophy (occupying more than 75% of the space between pillars); a right tonsil with 2+ hypertrophy (25% to 50% between pillars); mild erythema of the left tonsil with no exudates; uvular deviation to right; and posterior pharyngeal wall fullness. Neck examination showed bilateral cervical lymphadenopathy with significant swelling below the left mandibular angle. The rest of the examination findings were normal.
Results of a complete blood count and a basic metabolic panel were within normal limits and noncontributory. Radiographs of the neck (Figures 1 and 2) revealed severe prevertebral soft-tissue swelling with probable upper airway compromise. A computed tomography scan of the neck (Figure 3) showed a heterogeneous mass-like density in the left tonsillar bed, measuring 3.4 × 4.5 × 5.3 cm, extending into the peritonsillar and lateral pharyngeal spaces, with compromise of the upper airways to a moderate degree.
On admission, the patient’s stridor worsened and the oxygen desaturations continued. He was seen by an otorhinolaryngologist and taken to the operating room to obtain control of his airway and to obtain a biopsy of the mass. Tracheostomy was performed, and the patient placed on ventilator. Biopsy specimens were sent for pathology analysis.
On day 3 of the boy’s hospital course, flow cytometry results on the preliminary pathology report were negative for lymphoma, but showed a suspected small-round-blue-cell tumor. On day 5, the final pathology report results were positive for small-round-blue-cell tumor. Based on the histology, immunohistochemistry, and flow cytometry results, the tumor most likely was an undifferentiated neuroblastoma (NB).
Neuroblastomas arise from primitive sympathetic ganglion cells. They are heterogeneous and vary in location, histology, and biologic characteristics. They account for 97% of neuroblastic tumors and 8% of childhood malignancies overall.1 NB is a disease of children and is the third most common childhood cancer, following leukemia and brain tumors.1-3 NBs are the most common extracranial tumors in children and the most common cancer in infants younger than 1 year of age.1-3 In the United States, 600 cases are reported annually; NBs account for 15% of childhood cancer fatalities.1-3 The median age of patients at diagnosis is 17 months, and 40% of NBs are diagnosed before 12 months of age.1-3 NBs are slightly more common in boys and in the white population.1-3
Numerous risk factors are associated with NBs. Maternal risk factors include opiate consumption,4 folate deficiency,5 toxic exposures,2,6 and gestational diabetes.7 Other risk factors include the presence of Turner syndrome, Hirschsprung disease, central hypoventilation, neurofibromatosis type 1, and the anaplastic lymphoma receptor tyrosine kinase gene (ALK).8 However, the majority of cases are not associated with a particular risk factor or a specific germline. In 50% of cases, chromosomal deletions localized to 1p, 11q, and 14q are found.9 Deletion on 1p most commonly is associated with amplification of the MYCN oncogene, which is associated with a poorer prognosis.10
NBs have a broad range of clinical presentations. Some NBs spontaneously regress, others mature into benign ganglioneuromas, while still others progress to aggressive disseminated metastases. The clinical presentation depends largely on the location of the tumor.
The most common primary site is the adrenal glands, accounting for 40% of NBs.11 Abdominal tumors account for 25%, while 15% are thoracic tumors, 5% are cervical, and 5% are found in the pelvic sympathetic ganglia.11 The autonomic nervous system is less commonly affected, and 1% of primary sites cannot be identified.11 NBs are known to metastasize to lymph nodes, bone marrow, cortical bone, dura, orbits, liver, and skin.11 They less commonly metastasize to pulmonary or intracranial sites.11
Symptoms relate to the location of the tumor. Abdominal tumors cause abdominal pain, abdominal mass, or constipation.3 Orbital tumors can present with proptosis, periorbital ecchymosis, or even Horner syndrome. Other symptoms include but are not limited to airway compromise, back pain, weakness, bladder dysfunction, subcutaneous nodules, secretory diarrhea, fever, weight loss, anemia, hypertension, opsoclonus-myoclonus-ataxia syndrome, heterochromia iridis, and bone pain.12,13 The diagnostic criteria for NB require one of the following: either pathologic diagnosis from tumor tissue, or elevated serum urine catecholamines or elevated urinary catecholamine metabolites; or evidence of metastases to bone marrow and elevated serum urine catecholamines or elevated urinary catecholamine metabolites.3,14,15
Treatment and Prognosis
Treatment is based on the Children’s Oncology Group Neuroblastoma risk stratification system.10,16-18 It divides cases into low, intermediate, or high risk and is based on stage, the age of the patient at diagnosis, histology, quantitative DNA content of the tumor, and the presence or absence of MYCN oncogene amplification. The low-risk category includes stages 1, 2A, and 2B, which show no amplification of the MYCN oncogene and have a favorable histology. Intermediate risk includes patients whose NB is diagnosed before the age of 18 months, with stage 3 disease and with no amplification of the MYCN oncogene. It also includes patients with stage 4 disease that shows no amplification of the MYCN oncogene. High-risk cases are patients who are diagnosed with NB after 18 months of age and who have disseminated or localized disease with MYCN amplification.
Surgery is the mainstay treatment for patients in the low-risk category. However, expectant observation also is a reasonable alternative to surgery in newborns with localized disease or with asymptomatic stage 4S disease. If tumor enlargement is seen, surgery then is recommended. Chemotherapy is reserved for tumors that cannot be resected or cases of spinal cord compression, respiratory distress, or bowel compromise. Radiation is generally avoided overall and is reserved for unresectable tumors or tumors that are unresponsive to chemotherapy.19
Patients in the intermediate-risk group generally undergo chemotherapy for 12 to 24 weeks and tumor resection if possible. Radiation is used only in cases of life-threatening complications or if the tumor is unresponsive to chemotherapy.20 High-risk cases are treated with surgery and chemotherapy, and possibly with high-dose chemotherapy with hematopoietic stem-cell rescue and radiation therapy.21
Prognosis depends somewhat on the patient’s age at time of diagnosis but is based more on the stage and histology of the tumor. Most infants with disseminated disease have a favorable prognosis after chemotherapy and surgery.2,19 Children over 18 months of age with advanced NB have a poor prognosis despite intensive multimodality therapy.2,19 Low-risk patients have a 2-year event-free survival rate of 85% to 100%.2,19 Relapse is treated with further surgery or chemotherapy.
The prognosis of patients with intermediate risk depends largely on age at diagnosis and the histology of the tumor, but long-term survival is greater than 90%.20 High-risk patients are treated with multimodality therapy, which has increased the long-term survival rate from 15% to 40%.21 Research now is focused on maximizing the effects with stem-cell rescue and identifying the best chemotherapy agents.
Although NBs are not a common clinical presentation, they are important to consider in the workup of infants and children with a neck mass or who are in respiratory distress. Early recognition and diagnosis is important for better outcomes.
This case is significant because of the rarity of the clinical presentation and because it highlights the importance of considering a broad differential diagnosis that includes noninfectious causes of respiratory distress. The patient in this case received a diagnosis of poorly differentiated stage 3 NB of the neck. He was placed on high-risk protocol and underwent chemotherapy and radiation. He has been doing well and has been in remission for more than a year. n
Rhonda Graham, DO, is a third-year postgraduate pediatrics resident at Palms West Hospital in Loxahatchee, Florida.
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