History
Neuroblastoma has been called the great mimicker because of its myriad clinical presentations related to the site of the primary tumor, metastatic disease, and its metabolic tumor by-products. Sixty-five percent of primary neuroblastomas occur in the abdomen, with most of these occurring in the adrenal gland. As a result, most children present with abdominal symptoms, such as fullness or distension.
Obtaining a complete history and physical examination are paramount to an accurate diagnosis and subsequent management of neuroblastoma. Eliciting a history of the child's general appearance, recent trauma, changes in appetite and weight, and recurrent abdominal pain is important. Symptoms are usually related to either an abdominal mass or bone pain secondary to metastatic neuroblastoma. Reports of fatigue, bone pain, and changes in bowel or bladder habits may contribute to an accurate diagnosis. Physical findings might include hepatomegaly; blanching subcutaneous nodules; or a large, irregular, firm abdominal mass.
Typically, children with localized disease are asymptomatic, whereas children with disseminated neuroblastoma are generally sick and may have systemic manifestations, including unexplained fevers, weight loss, anorexia, failure to thrive, general malaise, irritability, and bone pain.
Physical Examination
The most common finding upon physical examination is a nontender, firm, irregular abdominal mass that crosses the midline. In contrast, children who present with Wilms tumor have a smooth mobile flank mass that typically does not cross the midline.
At diagnosis, the site of neuroblastoma is predictably age-dependent. Infants often present with compression of the sympathetic ganglia in the thoracic region, which might result, for example, in Horner syndrome (myosis, anhydrosis, and ptosis) or superior vena cava syndrome. Older children typically present with abdominal symptoms because, as stated above, more than 40% of neuroblastomas are adrenal in origin. Children who are preschool aged should have working differential diagnoses for an abdominal mass, including lymphoma, hepatoblastoma, rhabdomyosarcoma, renal cell carcinoma, and neuroblastoma.
More than 50% of patients who present with neuroblastoma have metastatic disease. The fact that many other syndromes related to metastatic neuroblastoma are also common in these patients is not surprising.
For example, Pepper syndrome occurs in infants with overwhelming metastatic neuroblastoma of the liver that results in respiratory compromise. Described by William Pepper in 1901, Pepper syndrome was identified as a localized primary tumor and metastatic disease limited to the skin, liver, and bone marrow in infants. Pepper syndrome has since been associated with stage 4S neuroblastoma, a unique entity that occurs only in infants younger than 1 year. Pepper syndrome generally confers a better prognosis, as it is associated with spontaneous regression. Some infants with stage 4S neuroblastoma, however, die of massive hepatomegaly, respiratory failure, and overwhelming sepsis.
"Blueberry muffin" babies are infants in whom neuroblastoma has metastasized to random subcutaneous sites. When provoked, the nodules become intensely red and subsequently blanch for several minutes thereafter. The response is probably secondary to the release of vasoconstrictive metabolic tumor by-products. These nodules can be diagnostic of neuroblastoma, but leukemic infiltrates that metastasize to the skin should be considered in the differential diagnoses when these children are evaluated.
Widespread metastasis of neuroblastoma to the bone may result in Hutchinson syndrome, which results in bone pain with consequent limping and pathologic fractures. Neuroblastomas that arise in the paraspinal ganglia may invade through the neural foramina, compress the spinal cord, and subsequently cause paralysis.
Infrequently, neuroblastoma can become metastatic to the retrobulbar region, leading to rapidly progressive, unilateral, painless proptosis; periorbital edema; and ecchymosis of the upper lid. This lesion often can be confused with trauma or child abuse. See the image below.
Most neuroblastomas produce catecholamines as metabolic by-products, which result in some of the most interesting presentations observed in children with neuroblastoma. For example, Kerner-Morrison syndrome causes intractable secretory diarrhea, resulting in hypovolemia, hypokalemia, and prostration. This syndrome is caused by vasoactive intestinal peptide (VIP) tumor secretion and is more commonly associated with ganglioneuroblastoma or ganglioneuroma. Kerner-Morrison syndrome typically resolves following the complete removal of the tumor.
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CT scan in a 2-week-old boy noted to have an abdominal mass on a prenatal sonogram. This postnatal abdominal CT scan revealed a left suprarenal mass with mass effect of the spleen.
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Abdominal CT scan in a 2-week-old boy noted to have an abdominal mass on a prenatal sonogram. A postnatal abdominal CT scan revealed a left suprarenal mass with mass effect of the spleen (see the previous image). This abdominal CT scan represents a more caudal view. Note the very large left mass with central necrosis. The mass effect of the spleen is apparent.
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A 2-week-old boy is noted to have an abdominal mass on prenatal ultrasound. A postnatal abdominal CT scan revealed a left suprarenal mass with mass effect of the spleen (see the first image above). A more caudal view revealed the very large left mass with central necrosis (see the second image above). This is a more caudal view of the CT scan than in the previous 2 images. The left kidney comes into view, as it is inferiorly displaced and laterally rotated by the large superior neuroblastoma.
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Bulky lymph nodes just medial to the left kidney.
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Upper periorbital edema, proptosis, and ocular ecchymosis in a 9-month-old girl.
