Neuroblastoma Imaging

Updated: Aug 05, 2015
  • Author: Steven West, DO; Chief Editor: Eugene C Lin, MD  more...
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Overview

Overview

Neuroblastoma is the most common extracranial pediatric neoplasm and the third most common pediatric malignancy after leukemia and central nervous system (CNS) tumors. In the first year of life, neuroblastoma accounts for 50% of all tumors. [1] Neuroblastoma is associated with a favorable prognosis, with most patients considered to be at low or intermediate risk for recurrence of the disease. [2] Neuroblastomas can arise from anywhere along the sympathetic chain. They have been associated with a number of disorders, such as Hirschsprung disease, fetal alcohol syndrome, DiGeorge syndrome, Von Recklinghausen disease, and Beckwith-Wiedemann syndrome. The radiologic characteristics of neuroblastomas are demonstrated in the images below.

Axial nonenhanced T1-weighted MRI shows a hypointe Axial nonenhanced T1-weighted MRI shows a hypointense mass in the retroperitoneum originating from the left adrenal gland. The mass displaces the left kidney in an anterolateral direction, it extends through the neuroforamen into the spinal canal, and it displaces the spinal cord to the right. The exact site of origin of large masses can be difficult to determine. Sympathetic-chain primaries supposedly invade the spinal canal with greater frequency than do adrenal primaries.
An intravenous pyelogram (IVP) shows an inferiorly An intravenous pyelogram (IVP) shows an inferiorly displaced kidney on the right. Above the right kidney are stippled calcifications. These findings are consistent with those of a neuroblastoma.
Nonenhanced axial CT scan of the chest in a patien Nonenhanced axial CT scan of the chest in a patient with a thoracic neuroblastoma shows a large, right posterior mediastinal mass extending into the spinal canal and displacing the cord laterally to the left.
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Radiography

Plain radiographs of the abdomen may show a flank mass. Stippled calcifications are present on up to 30% of radiographs. Hepatomegaly may occur secondary to metastatic involvement. Plain images of the chest often show a posterior mediastinal mass. Splaying of the ribs and rib erosion have been seen in patients with thoracic neuroblastomas due to the primary tumor. (See the images below.)

Frontal view of the chest shows a mass in the righ Frontal view of the chest shows a mass in the right thorax behind the heart. Posterior rib changes and the lateral view (seen in the next image) confirm that this is a posterior mediastinal mass. Note splaying and thinning of the ribs in the lower rib cage on the right. This was a thoracic neuroblastoma.
Lateral view of the chest in the same patient as i Lateral view of the chest in the same patient as in the previous image confirms the posterior mediastinal mass.

Pleural effusions and pleural nodules have been seen on chest radiographs. Lung parenchymal metastases are rarely seen on radiographs but are often detected on autopsy. Widening of the paraspinal line can be seen secondary to retrocrural extension of retroperitoneal neuroblastomas.

Bone metastases (seen in the images below) usually occur in the long bones and typically present as irregular lucencies or lytic lesions in the metaphysis or submetaphyseal bone.

Anteroposterior (AP) views of both knees show irre Anteroposterior (AP) views of both knees show irregular lucencies in both distal femoral and proximal tibial metaphyses; these represent relatively symmetrical metastatic disease.
Image shows a destructive metastatic lesion involv Image shows a destructive metastatic lesion involving the proximal fibular metaphysis with periosteal reaction in the proximal fibular diaphysis.

Lytic lesions may be seen in skull, ribs, and pelvis. Sclerotic lesions have been seen and may be secondary to tumor infarction. Periosteal reaction is common. Widening of the cranial sutures secondary to dural metastasis (demonstrated in the first 2 images below) can be seen in neuroblastoma. The classic hair-on-end appearance (seen in the third image below), albeit unusual in neuroblastoma, can be seen in the skull in destructive lesions.

Anteroposterior (AP) or preorbital view of the sku Anteroposterior (AP) or preorbital view of the skull shows widening of the sagittal and lambdoid sutures. This finding is due to dural metastases.
Lateral view of the skull shows widening of the co Lateral view of the skull shows widening of the coronal sutures and multiple lucencies in the parietal and frontal bones of the skull in this patient with metastatic neuroblastoma.
Classic hair-on-end appearance of a destructive me Classic hair-on-end appearance of a destructive metastatic lesion of the skull.

Intraspinal extension of neuroblastomas can be seen on radiographs. Lateral views of the spine may show widening of the neuroforamina. Vertebral-body scalloping, erosion of the pedicles, and scoliosis have also been seen in patients with intraspinal involvement. Intraspinal involvement may be present in the absence of these findings, and magnetic resonance imaging (MRI) is far superior in evaluating for intraspinal involvement.

Intravenous pyelography (IVP) and excretory urography were widely used in the past to evaluate patients with adrenal neuroblastomas before the advent of computed tomography (CT), MRI, and ultrasonography. [3] Adrenal neuroblastomas typically displace the ipsilateral kidney laterally and downward, producing the classic drooping-lily sign on excretory urograms (as seen in the image below). The drooping-lily sign is also caused by an obstructed upper moiety of a duplex collecting system.

Intravenous pyelogram (IVP) shows a classic droopi Intravenous pyelogram (IVP) shows a classic drooping-lily sign involving the right kidney. This patient had a known right adrenal neuroblastoma.
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Computed Tomography

CT scanning is the modality most commonly used to diagnose and stage neuroblastomas. CT can show the organ of origin, extent of the tumor, lymphadenopathy, metastases, and calcifications. About 80-90% of neuroblastomas show stippled calcifications on CT. (See the images below.) [4, 5]

Nonenhanced axial CT scan of the chest in a patien Nonenhanced axial CT scan of the chest in a patient with a thoracic neuroblastoma shows a large, right posterior mediastinal mass extending into the spinal canal and displacing the cord laterally to the left.
This patient has enhancing dural metastases near t This patient has enhancing dural metastases near the frontal and occipital lobes. This finding could result in widening of the sagittal suture on plain images of the skull.
Axial CT scan of the orbits shows a heterogeneous- Axial CT scan of the orbits shows a heterogeneous-appearing, metastatic soft-tissue mass in the right orbit that displaces the globe and lateral rectus muscle medially. This patient presented with proptosis of the right eye.
Axial CT scan of the orbits in the same patient as Axial CT scan of the orbits in the same patient as in the previous image, obtained a few millimeters cephalic, shows calcifications in the left orbital mass.
Bone window in a patient with bilateral proptosis Bone window in a patient with bilateral proptosis shows osseous destruction involving both lateral orbital walls (left to right).
Bone-window axial CT study of the orbits (same pat Bone-window axial CT study of the orbits (same patient as in the previous image) shows extensive bony destruction involving both frontal bones.
Coronal CT scan of the orbits and sinuses shows a Coronal CT scan of the orbits and sinuses shows a large, enhancing, and expansile mass occupying the ethmoid air cells that is invading the cribriform plate and breaking through to the left anterior cranial fossa. This entity is known as an esthesioneuroblastoma. Image courtesy of Michael Lev, MD.

Neuroblastomas often encase or compress adjacent blood vessels. Vessels that are commonly engulfed are the inferior vena cava, the renal veins and arteries, the splenic vein, the aorta, the celiac artery, and the superior mesenteric artery. Neuroblastomas rarely invade into the lumen of blood vessels.

The tumors often appear lobulated and typically have a heterogeneous appearance on contrast-enhanced CT. There are areas of low attenuation in the mass secondary to necrosis and hemorrhage. CT is good for detecting lung metastases and focal liver metastases (which appear as focal hypoattenuating and poorly enhancing masses). [6] Bone-window settings should always also be examined to assess for skeletal metastases.

False positives/negatives

Diffuse liver metastases may be missed on CT. Cerebral metastases can appear as enhancing meninges secondary to dural metastases, which can simulate meningitis. Sometimes, brain metastases can appear as cystic lesions with peripheral enhancement, which can mimic an abscess. CT is poor for detecting metastatic disease to the bone and is limited in evaluating extradural extension of tumor into the spinal canal without the aid of intrathecal contrast material (CT myelography).

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Magnetic Resonance Imaging

MRI has a number of advantages over CT. One is that MRI does not use ionizing radiation. Other advantages include the multiplanar imaging capabilities of MRI and, often, the elimination of the need to use intravenous contrast enhancement. [5]

MRI utilizes the intrinsic tissue characteristics on T1- and T2-weighted imaging. Neuroblastomas are typically hypointense on T1-weighted images and hyperintense on T2-weighted images. When contrast material is administered, the tumor exhibits inhomogeneous enhancement. Calcifications appear as signal voids on MRIs. Hemorrhagic areas often appear bright on T1-weighted images.

Bone-marrow disease appears bright (hyperintense) and heterogeneous on T2-weighted images and dark (hypointense) on T1-weighted images. Diffuse liver metastases appear bright on T2-weighted MRIs. [7]

The characteristics of neuroblastomas on T1- and T2-weighted MRI scans are demonstrated in the images below.

Axial nonenhanced T1-weighted MRI shows a hypointe Axial nonenhanced T1-weighted MRI shows a hypointense mass in the retroperitoneum originating from the left adrenal gland. The mass displaces the left kidney in an anterolateral direction, it extends through the neuroforamen into the spinal canal, and it displaces the spinal cord to the right. The exact site of origin of large masses can be difficult to determine. Sympathetic-chain primaries supposedly invade the spinal canal with greater frequency than do adrenal primaries.
Axial T2-weighted MRI in the same patient as in th Axial T2-weighted MRI in the same patient as in the previous image again demonstrates extradural extension into the spinal canal. The tumor appears hyperintense. Spinal cord displacement is better demonstrated on T2-weighted images than on other images.
Sagittal T2-weighted MRI in the same patient as in Sagittal T2-weighted MRI in the same patient as in the previous 2 images shows a hyperintense extradural mass in the lower thoracic spine. Axial and coronal images confirm that this is extradural extension of a neuroblastoma of the left adrenal gland.
Coronal T2-weighted MRI in the same patient as in Coronal T2-weighted MRI in the same patient as in the previous 3 images shows a hyperintense mass in the left adrenal gland. The mass is extending cephalad into the spinal canal via the neuroforamen.
Axial T2-weighted chest MRI in a patient with a th Axial T2-weighted chest MRI in a patient with a thoracic neuroblastoma shows a large, right posterior mediastinal mass extending into the spinal canal and displacing the cord laterally to the left. The mass is hyperintense on T2-weighted images.
Sagittal T2-weighted MRI in a patient with a thora Sagittal T2-weighted MRI in a patient with a thoracic neuroblastoma shows a large, hyperintense, right posterior mediastinal mass extending into the spinal canal through multiple neuroforamina.

Degree of confidence

MRI is superior to CT in evaluating extradural extension of the tumor and bone marrow involvement and in identifying diffuse hepatic metastases. MRI can show displacement of the spinal cord and/or nerve root displacement or compression and epidural spread of neuroblastoma exceptionally well. MRI results are well correlated with findings from bone marrow biopsy.

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Ultrasonography

Neuroblastomas appear as an inhomogeneously echogenic mass on sonograms, as seen in the image below. Calcifications typically appear as focal brightly echogenic areas in the mass. In masses with fine calcifications, images show diffuse, increased echogenicity. Acoustic shadowing from the calcifications may or may not be present. Hemorrhagic or necrotic areas in the tumor appear as hypoechoic or anechoic areas.

Transverse sonogram of the left renal area was obt Transverse sonogram of the left renal area was obtained in a toddler who presented with abdominal pain and a palpable mass in the left flank. Sonogram shows an inhomogeneously hyperechoic, extrarenal mass that laterally displaces the kidney (which appears as a relatively hypoechoic structure).

Ultrasonography can be used as a screening tool for detecting abdominal or pelvic masses in children. Doppler ultrasonography can be used to identify blood flow through blood vessels encased or compressed by the tumor. Increased vascularity of neuroblastomas has been reported on Doppler sonograms, although typically most lesions show reduced vascularity.

Obstetric ultrasonography can depict fetal neuroblastomas as early as 19 weeks' gestational age. Most of the cases identified during obstetric ultrasonography are diagnosed during the third trimester (around 36 weeks).

Ultrasonography is used to differentiate adrenal hemorrhage from neuroblastoma. Adrenal hemorrhage is the most common cause of adrenal mass in the neonatal population. It typically appears echogenic in the newborn, as neuroblastomas do, but gradually becomes anechoic and avascular and often becomes smaller on serial sonograms as it regresses.

Degree of confidence

Sonograms can depict liver metastases, but they are limited in assessing the extent of metastatic disease to the liver. This is better evaluated with CT scanning or MRI, although all of these techniques may be complementary (eg, a metastasis may be visible on sonograms but not on CT scans, or vice versa).

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Nuclear Imaging

Bone scans obtained by using technetium-99m (99m Tc) methylene diphosphate (MDP), an example of which appears below, are performed in many patients with neuroblastoma to assess metastatic disease. Approximately 74% of primary tumors in neuroblastoma take up99m Tc MDP. Uptake may be seen in liver and lung metastases as well.

Technetium-99m methylene diphosphate (MDP) bone sc Technetium-99m methylene diphosphate (MDP) bone scan shows a focus of intense activity in the left lower quadrant of the abdomen adjacent to the spine, above the bladder. This finding corresponds to a neuroblastoma in this location. Image shows activity in the dilated renal calyces on the left, which suggests partial obstruction of the left ureter by the mass. No evidence of metastatic disease is observed.

99m Tc MDP scans cannot be used to differentiate between cortical and bone marrow metastases; this limits their usefulness in accurately staging the disease, particularly in differentiating stage 4 from stage 4s neuroblastomas in the Evans classification system. In stage 4, distant metastases are present. Stage 4s occurs in infants who have a localized tumor that does not cross the midline, with metastatic disease confined to the liver, skin, and bone marrow and with no evidence of cortical bone involvement observed. [8]

Iodine-131 (131I) metaiodobenzylguanidine (MIBG) and iodine-123 (123I) MIBG [9] are used to identify sites of primary neuroblastomas. Tumors that contain sympathetic tissue, such as neuroblastomas, ganglioneuroblastomas, ganglioneuromas, medullary thyroid carcinomas, pheochromocytomas, and carcinoids, take up MIBG. However, MIBG scanning cannot be used to differentiate these lesions. In the age group in which neuroblastoma (and its more benign forms, ganglioneuroblastoma and ganglioneuroma) is prevalent, the other tumors are rare. In patients with high-risk neuroblastoma, Papathanasiou et al found that 123I MIBG was superior to fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in assessing extent of disease. [10, 11, 12, 13, 14]

MIBG has also been used to follow up the response to treatment in neuroblastoma patients. One of the drawbacks of using MIBG is that up to 30% of neuroblastomas may not take up MIBG, although 95% of neuroblastomas secrete catecholamines. Also, up to 50% of recurrent neuroblastomas do not take up MIBG even if they did so before therapy. [15]

131 I MIBG has a high principal proton energy (364 KeV). It emits beta particles, thus giving a large dose of radiation to the patient.123 I MIBG has a lower principal photon energy (159 KeV). It also does not emit beta particles, giving less radiation dose to the patient.123 I MIBG has a shorter half-life (13 h) than that of131 I MIBG (8 d), and it must be used the day it is produced, making it more expensive and less readily available.

In a retrospective study of 28 patients with neuroblastoma, PET/CT was found to be superior to I-MIBG (iodine-131 metaiodobenzylguanidine) scintigraphy in detecting lymph node and bone/bone marrow lesions. Sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of F-FDG PET/CT were 100%, 60%, 92%, 100%, and 92.80%, respectively; and those of I-MIBG were 95.65%, 60%, 91.67%, 75%, and 89.20%, respectively. In these patients, PET/CT detected 107 lesions, and I-MIBG scintigraphy detected 74 lesions. [16]

Another isotope that can be used in detecting primary neuroblastomas is indium-111 (111In) pentetreotide, which is a somatostatin analogue. Studies have shown that it is as sensitive as MIBG in detecting neuroblastoma and other catecholamine-secreting tumors.111 In pentetreotide has 2 principal photon energies (174 and 245 KeV), both of which are lower than that of 131I MIBG. It also does not emit beta particles, giving a lower radiation dose to the patient.111In pentetreotide also requires less patient preparation and produces images with better resolution than MIBG images have on gamma scintillation cameras, but it is not widely used in pediatric oncology imaging.

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