Metastatic neuroblastoma

Findings

The initial computed tomography (CT) scan showed extra-axial and calvarial lesions that encased the brain parenchyma of both cerebral hemispheres, producing some separation of the calvarial sutures (Figure 1A and B). No intra-axial lesions were identified at that time, except the right lateral extraconal orbital involvement (Figure 1C).

Four months later, a follow-up study revealed significant interval progression of the disease. There was an increase in size of the extra-axial metastases, with diffuse permeative calvarial bone destruction and periosteal reaction. The sutures were now widely separated because of the mass effect of the metastases (Figure 2A). Additionally, the scan revealed the development of a large right frontal lobe hematoma, with extension into the ventricles. Subsequent midline shift with subfalcine herniation was present (Figure 2B). Further tumor progression was evidenced by bilateral extraconal orbital extension, causing bilateral proptosis (Figure 2C).

Discussion

Neuroblastoma is the most common solid abdominal mass in infancy and the third most common overall malignancy, following leukemia and CNS tumors in children. The median age of diagnosis is 22 months.¹ Neuroblastomas arise from neural crest tissue and can thus be found anywhere along the sympathetic chain. The most common area of involvement is the adrenal gland, where approximately one third of these tumors are located. The second most common area is the extra-adrenal retroperitoneum, followed by the posterior mediastinum.² Much less common sites include the neck and pelvis (organ of Zuckerkandl).³

Clinical presentation depends on the extent and location of disease. Most patients present with an abdominal mass, which may be accompanied by constitutional symptoms of fever, weight loss, and malaise. Since neuroblastoma has the propensity for increased catecholamine production, symptoms may include flushing, hypertension, diaphoresis, tachycardia, intractable diarrhea, and hyperglycemia. If the tumor invades the neural foramina and compresses a nerve, peripheral nerve deficits can appear. Orbital metastatic disease may result in proptosis or ecchymosis. Additionally, more than half of neuroblastoma patients have osseous metastatic disease at the time of diagnosis, which can manifest as Hutchinson syndrome if limping and irritability are present.¹

CT is the most common modality for radiographic assessment of neuroblastoma. Typical findings include a large, irregularly shaped, heterogeneous adrenal mass, which often contains areas of necrosis, hemorrhage, and calcification.³ The tumor has a tendency to infiltrate around regional structures rather than displace them.¹ Adenopathy and vascular encasement without actual invasion are also characteristic findings.¹ Other radiographic manifestations of the disease depend on tumor origin and extent and location of disease.

Unfortunately, metastatic disease is common in neuroblastoma, often causing symptoms that prompt medical attention. Common places for neuroblastoma to metastasize to are cortical bone, bone marrow, and lymph nodes. In addition, orbital, liver, and skin metastases are frequently observed, which may lead to proptosis, hepatomegaly, and dark blue skin masses (also known as "blueberry muffin syndrome"), respectively. Less common areas of metastatic disease include the dura mater, lung, and brain.² Usually, if intra-axial CNS involvement is seen, it is a result of an extension from extra-axial lesions (eg, from the dura or orbits).^2,4-6 Isolated parenchymal disease is rare, although the incidence has been rising with the introduction of improved chemotherapeutic regimens and observed prolonged survival rates.^2,5

The patient in this case demonstrated the classic radiographic findings of metastatic CNS disease, which was originally exclusively in the extra-axial compartment and manifested as extensive dural metastases. On the subsequent head CT, the expected findings of progressive disease were shown with increased dural metastastic bulk, intra-axial extension with cerebral and intraventricular hemorrhage, and orbital metastases that caused proptosis. The impressive sutural diastases were sequelae of the growing dural metastases that exerted progressively increasing pressure at the suture line.⁵ If this feature is seen on imaging, the differential diagnosis is short and includes metastatic neuroblastoma, leukemia, and lymphoma.¹

Survival rates depend on the staging of disease. Stage I tumors are limited to the organ of disease without metastases. Stage II tumors have spread locally but have not crossed the midline. Stage III tumors have extended across the midline. Stage IV tumors show evidence of distant metastatic disease. A special subset of stage IV has been designated as stage IVS, which has distant metastases to the liver, skin, and bone marrow, without evidence of skeletal metastases in children younger than 1 year. Stage IVS infers a much better prognosis, similar to that of stage I disease.⁵

CONCLUSION

Neuroblastoma CNS metastates are not uncommon to the dura or orbits. Common CT manifestations include dural infiltration of the disease, which may lead to sutural diastasis. When this finding is present, the differential includes metastatic neuroblastoma, lymphoma, and leukemia. Orbital metastatic disease usually presents as a mass in the extraconal space with resultant proptosis. If intra-axial extension occurs, hemorrhage is often present within the tumor. CNS metastatic disease is stage IV neuroblastoma, which infers a poor prognosis.

1. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: Radiologic-pathologic correlation. RadioGraphics. 2002;22:911-934.
2. Astigarraga I, Lejarreta R, Navajas A. Secondary central nervous system metastases in children with neuroblastoma. Med Pediatr Oncol.1996;27:529-533.
3. Rha SE, Byun JY, Jung SE, et al. Neurogenic tumors in the abdomen: Tumor types and imaging characteristics. RadioGraphics.2003;23:29-43.
4. Gallet BL, Egelhoff JC. Unusual CNS and orbital metastases of neuroblastoma. Pediatr Radiol.1989;19:287-289.
5. Zimmerman RA, Bilaniuk LT. CT of primary and secondary craniocerebral neuroblastoma. AJR Am J Roentgenol.1980;135:1239-1242.
6. Koizumi JH, Dal Canto MC. Retroperitoneal neuroblastoma metastatic to brain. Report of a case and review of the literature. Childs Brain. 1980;7:267-279.