Clinical Presentation
Other markers
These markers are not used to help determine risk groups at this time, but they are still important and may influence a doctor's decision on how to treat a child with neuroblastoma.
Chromosome changes –tumor cells that are missing certain parts of chromosomes 1 or 11 (known as 1p deletions or 11q deletions) may predict a less favorable prognosis. It is thought that these chromosome parts, which are missing in many neuroblastomas, may contain important tumor suppressor genes, but more studies are needed to verify this.
Having an extra part of chromosome 17 (17q gain) is also linked with a worse prognosis. This probably means that there is an oncogene in this part of chromosome 17.
Understanding the importance of chromosome deletions/gains is an active area of neuroblastoma research.
Neurotrophin (nerve growth factor) receptors – these are substances on the surface of normal nerve cells and on some neuroblastoma cells. They normally allow the cells to recognize neurotrophins – hormone-like chemicals that help the nerve cells to mature.
Neuroblastomas that have more of certain neurotrophin receptors, especially the nerve growth factor receptor called TrkA, may have a better prognosis.
Serum markers – serum (blood) levels of certain substances can be used to help predict prognosis.
Neuroblastoma cells release ferritin, a chemical that is an important part of the body's normal iron metabolism, into the blood. Patients with high ferritin levels tend to have a worse prognosis.
Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are made by some types of normal cells as well as by neuroblastoma cells. Increased levels of NSE and LDH in the blood are often linked with a worse outlook in children with neuroblastoma.
Tumors arise anywhere there are sympathetic nerves from the brain to the pelvis. Neuroblastoma is a tumor with multiple clinical manifestations related to the site of the primary tumor, the presence of metastases, and the production of certain metabolic tumor byproducts.
Most primary tumors occur in the abdomen (65%). The tumor may be hard, nodular, fixed, and painful on palpation. The frequency of adrenal tumors is slightly higher (40%) in children compared to infants (25%). Infants have more thoracic and cervical primary tumors.
The clinical presentation depends on the location of the primary. Often the symptoms are few and general. Generalized symptoms include weight loss, failure to thrive, abdominal pain and distention, fever, and anemia.
Neoplasms arising in the upper mediastinum or neck may involve the stellate ganglion (or cervicothoracic ganglion or inferior cervical ganglion - is a sympathetic ganglion) and cause Horner’s syndrome, which is characterized by ptosis (drooping of the upper eyelid from loss of sympathetic innervation to the superior tarsal muscle); miosis (small pupils); enophthalmos, anhidrosis (decreased sweating on the affected side of the face); and heterochromia of the iris on the affected side.
Those with thoracic primaries are diagnosed after a mass is found on a routine chest radiograph. The parents often find abdominal tumors when they are bathing the child. Abdominal tumors are more irregular than Wilms’ tumors and more often cross the midline. Pelvic tumors may result in obstructive symptoms (urethral or colonic). Rarely they compress or infiltrate the iliac veins and/or arteries and present with lower extremity edema. Tumors that extend intraspinal in any of these locations may present with neurologic symptoms.
Hypertension is found in 25% of cases and is related to the production of catecholamines by the tumor.
Acute cerebellar ataxia, characterized by opsomyoclonus and nystagmus ("dancing eye syndrome"), has been observed. This syndrome is seen more frequently (> 60%) in patients with primary mediastinal tumors.
Rarely, patients with neuroblastoma present with profuse watery diarrhea if the tumor secretes vasoactive intestinal peptide (VIP). The diarrhea resolves once the tumor is removed.
90-95% of tumors are biologically active secreting vanillymandelic acid (VMA) or homovanellic acid (HVA) or other catecholamine metabolites. HVA represents degradation products of the dopamine pathway. More differentiated tumors produce norepinephrine and epinephrine that give rise to VMA. The VMA:HVA ratio has some prognostic implication with levels > 1 indicating tumors with a more favorable prognosis. 10% of neuroblastomas secrete acetylcholine and not catecholamines; these tumors tend to be more malignant.
Neuroblastoma may spread by direct extension into surrounding structures, lymphatic infiltration, or hematogenous metastases. Regional and distant lymph nodes, liver, bone marrow, and bone cortex are frequently involved.
Patients with bone cortex metastases have an ominous prognosis. Bone metastases occur in sites containing red marrow and involve the metaphyseal areas of long bones in addition to the skull, vertebral column, pelvis, ribs, and sternum. Bone lesions may cause extreme pain and may be first identified when a child refuses to walk because of leg pain.
Hematogenous metastases to the brain, spinal cord, and heart are unusual. Brain metastases usually manifest in older children with headaches and seizures. Lung metastases are found on chest radiographs in only 4% of patients. This may be the result of direct extension to the lung from mediastinal lymph nodes or diffuse hematogenous spread, presenting with a radiographic pattern that may be confused with pulmonary edema or interstitial pneumonia. Lung involvement by intralymphatic metastases (not seen on chest radiographs) may be noted at autopsy. Occasionally, patients with advanced disease present with a bleeding diathesis related to thrombocytopenia from extensive involvement of bone marrow and interference with hepatic production of clotting factors by liver metastases. Multiple subcutaneous skin nodules and hepatomegaly may occur in infants with stage IV-S neuroblastoma.
Metastases to the bony orbit may produce proptosis or bilateral orbital ecchymosis – often referred to as "panda eyes" or "raccoon eyes".