Neuroblastoma

Key Features

Essentials of Diagnosis

• Clinical manifestations vary with the primary site of malignant disease and the neuroendocrine function of the tumor

• Presence of constitutional symptoms such as fever, weight loss, and irritability

• Bone pain suggests metastatic disease, which is present in 60% of children older than 1 year

General Considerations

• Arises from neural crest tissue of the sympathetic ganglia or adrenal medulla

• Composed of small, fairly uniform cells with little cytoplasm and hyperchromatic nuclei that may form rosette patterns.

• Accounts for 7–10% of pediatric malignancies and is the most common solid neoplasm outside the CNS

• Fifty percent of neuroblastomas are diagnosed before age 2 years and 90% before age 5 years

Clinical Findings

Symptoms and Signs

• Fever, weight loss, and irritability

• Firm, fixed, irregularly shaped mass that extends beyond the midline

• Margins are often poorly defined

• Most children have an abdominal primary tumor (40% adrenal gland, 25% paraspinal ganglion)

• Tumor in the posterior mediastinum

  • Usually asymptomatic

  • Often discovered on a chest radiograph obtained for other reasons

• Cervical neuroblastoma

  • Presents as neck mass, which is often misdiagnosed as infection

  • Horner syndrome (unilateral ptosis, myosis, and anhidrosis) or heterochromia iridis (differently colored irises) may accompany tumor

• Paraspinous tumors

  • Can extend through the spinal foramina, causing cord compression

  • May present with paresis, paralysis, and bowel or bladder dysfunction

• Neuroblastoma has a predilection for metastasis to the skull, in particular the sphenoid bone and retrobulbar tissue; causes periorbital ecchymosis and proptosis

• Liver metastasis, particularly in the newborn, can be massive

• Neuroblastoma may also be associated with unusual paraneoplastic manifestations, such as opsoclonus-myoclonus, also called dancing eyes/dancing feet syndrome

  • This phenomenon is characterized by

    • Acute onset of rapid and chaotic eye movements

    • Myoclonic jerking of the limbs and trunk

    • Ataxia

    • Behavioral disturbances

  • Often persists after therapy is complete

  • Thought to be secondary to cross-reacting antineural antibodies

Differential Diagnosis

• Ewing sarcoma

• Rhabdomyosarcoma

• Peripheral neuroectodermal tumor

• Lymphoma

Diagnosis

Laboratory Findings

• Anemia

  • Present in 60% of children with neuroblastoma

  • Can be due to chronic disease or marrow infiltration

• Occasionally, thrombocytopenia is present

• However, thrombocytosis is a more common finding, even with metastatic disease in the marrow

• Urinary catecholamines are elevated in at least 90% of patients at diagnosis and should be measured prior to surgery

Imaging

• Plain radiographs of the primary tumor

  • May show stippled calcifications

  • Metastases to bone appear irregular and lytic

  • Periosteal reaction and pathologic fractures may also be seen

• CT scanning

  • Provides more information, including the extent of the primary tumor, its effects on surrounding structures, and the presence of liver and lymph node metastases

  • Classically, in tumors originating from the adrenal gland, the kidney is displaced inferolaterally, which helps differentiate ...