March 26, 2020
A 17-month-old boy referred for work-up of left eye deviation and right hip pain
Metastatic Neuroblastoma
- Background:
- Neuroblastomas are the third most common childhood cancer and the most common solid extracranial tumor diagnosed during the first 2 years of life, with a median age at diagnosis of 15–17 months.
- Neuroblastomas are tumors of primitive neural tissue and can arise anywhere along the sympathetic chain, with most primary tumors originating in the adrenal gland.
- Common sites of metastatic spread include bone, liver, and local lymph nodes, with skull metastases found in up to 25% of patients with neuroblastoma.
- Clinical Presentation:
- A classic presentation of primary tumor is abdominal distension and/or a firm, irregular abdominal mass that does cross the midline of the abdomen (in contrast to a Wilms tumor).
- Symptoms of metastases to the skull may include bruising of the area around the eyes, bulging eyes, and uncontrolled eye movement.
- Key Diagnostic Features:
- Classically presents with lytic bone lesions on plain films or CT, but less commonly presents with expanded diploe and spiculated periostitis—the so-called “hair-on-end” sign. Associated skull thickening and sutural widening may also be present.
- CT of the abdomen may demonstrate a heterogeneous soft-tissue mass, with over 80% of tumors presenting with calcification. These masses are iso- to hypointense on T1 MR imaging and hyperintense on T2 sequences.
- Metaiodobenzylguanidine (MIBG) nuclear medicine scans localize catecholamine-secreting tissues and are 88% sensitive and 99% specific for neuroblastoma.
- Histopathologically, neuroblastomas are round blue cell tumors with interspersed Homer Wright rosettes, with a majority demonstrating amplification of the N-myc oncogene (a poor prognostic factor).
- Differential Diagnoses:
- Hemolytic anemia, thalassemia, sickle cell disease: A majority of cases in which the ”hair-on-end” pattern is seen in the skull are due to anemias and hemoglobinopathies. Red marrow hyperplasia can lead to expansion of the diploic space reflecting increased medullary erythropoiesis. The "hair-on-end" pattern is seen in up to 8% of patients with beta thalassemia major and up to 5% of patients with sickle cell disease. However, lab work-up and newborn screen ruled out anemia in this case and a CT of the abdomen would later reveal a primary lesion in the retroperitoneum arising from the left adrenal gland.
- Skull hemangioma: The ”hair-on-end” pattern of periostitis may be seen in patients with skull hemangioma. CT of the head would also show a sharply marginated, expansile skull lesion.
- Cyanotic congenital heart disease: Uncorrected congenital heart diseases can cause red marrow hyperplasia in a similar fashion to the anemias that are described above. The patient in this case did not exhibit any symptoms consistent with cyanotic heart disease, and primary presentation of a cyanotic cardiac condition at age 17 months would be unusual.
- Leukemia: Can have a similar presentation on head CT, but is often accompanied by a subgaleal or epidural tumor, which was not seen in this case
- Treatment:
- Treatment of metastatic neuroblastoma is stratified by stage and risk. Poor prognostic factors include age > 18 months at diagnosis and N-myc amplification.
- Small, low-risk tumors are managed with observation or surgery without chemotherapy. Intermediate-risk tumors are managed with chemotherapy (doxorubicin, cyclophosphamide, and etoposide) followed by resection. With long-term survival of <15%, high-risk neuroblastoma is treated with resection and more aggressive chemotherapy.
- Radiation is reserved for progressive tumors that do not respond to chemotherapy.
