A father reports his 3-year-old daughter has decreased energy, loss of appetite, and an enlarging abdomen over the past few weeks. Intermittent emesis began yesterday. Physical examination reveals pallor, proptosis, periorbital discoloration, and a large, irregular abdominal mass along her left flank that crosses the midline. Her vital signs and the remainder of her examination are normal.
What is the most likely diagnosis?
What is the next step in evaluation?
ANSWERS TO CASE 45: Neuroblastoma
Summary: A toddler with fatigue, decreased appetite, periorbital discoloration, and a multiquadrant abdominal mass.
• Most likely diagnosis: Neuroblastoma.
• Next step in evaluation: Select laboratory testing and imaging to ascertain tumor genetic characteristics, location and extent, and impact on surrounding structures. Resultant staging and risk stratification help guide decision-making regarding perisurgical chemotherapy and/or irradiation.
1. Recognize the signs and symptoms of neuroblastoma.
2. Describe the diagnosis and treatment of neuroblastoma.
Since neuroblastoma origin and progression vary from patient to patient and a mass may not always be readily apparent on examination, clinicians must perform thorough histories and comprehensive examinations to ensure timely and accurate diagnosis and diminish the potential for metastatic disease at discovery. The diagnostic evaluation includes questioning and examining for syndromes associated with neuroblastoma.
HORNER SYNDROME: Characterized by eyelid ptosis and sluggish pupillary reflex; related to sympathetic nervous system dysfunction.
PARANEOPLASTIC SYNDROME: Characterized by hypertension and secretory diarrhea; related to tumor production of catecholamines and vasoactive intestinal peptide.
OPSOCLONUS-MYOCLONUS SYNDROME: Characterized by chaotic eye movements and myoclonic jerks; described as “dancing eyes, dancing feet” related to autoantibodies produced against neuronal elements.
Neuroblastoma is comprised of primitive neuroendocrine tissue. Its etiology is poorly understood, but believed to be multifactorial. It is the most prevalent solid, extracranial tumor in children and accounts for more than half of all cancers in infancy. Most arise in the abdomen from the adrenal gland, with other origins including intrathoracic and paraspinal neuronal ganglia.
Signs and symptoms related to neuroblastoma depend on tumor location; cervical ganglia tumors may cause Horner syndrome, intrathoracic tumors (most commonly seen in infancy) may be associated with wheezing and respiratory distress, and paraspinal tumors may cause compressive neuralgias, back pain, and urinary or stool retention. Abdominal masses are typically nontender, irregular, and cross the midline. Dependent on a tumor’s location and impact on surrounding structures, intrathoracic or paraspinal decompressive surgery may emergently be required.
Metastatic disease typically involves the skin, lungs, liver, and bone. Bluish skin discoloration (most often seen in infancy) represents subcutaneous infiltration. Pulmonary involvement can promote increased work of breathing, dyspnea, and pneumonia. Bone marrow infiltration may cause bone pain and pancytopenia; petechiae, bruising, pallor, and fatigue may occur. If the orbital bones are involved, proptosis and bluish periorbital discoloration, described as “raccoon eyes,” may be noted. Generalized lymphadenopathy also is common. Some patients develop paraneoplastic syndrome related to tumor neuroendocrine mediators, or opsoclonus-myoclonus syndrome (an autoimmune-mediated phenomenon that may be characterized by cerebellar ataxia).
The major differential diagnostic consideration is Wilms tumor. These tumors typically are associated with hematuria, hypertension, and a localized abdominal mass that rarely crosses the midline. In general, patients with neuroblastoma are slightly younger and sicker than patients with Wilms tumor.
Computed tomography (CT) or magnetic resonance imaging (MRI) is useful in identifying and assessing the extent of neuroblastoma. Laboratory markers include elevated urinary vanillylmandelic acid and homovanillic acid levels (catecholamine metabolites), observed in approximately 90% of neuroblastoma patients; other markers include elevated enolase, ferritin, and lactate dehydrogenase levels.
Treatment involves surgical excision of the tumor, usually after chemotherapy and/or radiotherapy to decrease tumor size. Combined multi-agent chemotherapy and radiotherapy often is used in patients with advanced-stage neuroblastoma. Staging is classically dependent on tumor location and extent, with risk assessment and therapeutic decision-making based on variables such as age at diagnosis and staging (eg, stage 2 disease localized to the abdomen of a 1-year-old requiring only limited postexcision chemotherapy versus stage 4 disease with bony metastases in a toddler mandating multi-agent chemotherapy and bone marrow transplantation). Other therapies under investigation include monoclonal antibody immunotherapy and radionuclide therapy.
Overall cure rates for neuroblastoma can exceed 90%, with infants typically having a better prognosis than older children. Select features, such as skeletal metastases or N-myc oncogene amplification at the cellular level, often denote a poor prognosis.
45.1 A mother recently feels a mass in the abdomen of her 4-year-old son during a bath, and brings him to your clinic for evaluation. He has no history of emesis, abnormal stooling, or abdominal pain. Physical examination reveals a resting blood pressure of 130/88 mm Hg, heart rate of 82 beats/minute, pallor, and a firm left-sided abdominal mass that doesn’t cross the midline. Which of the following is the most likely explanation for these findings?
D. Wilms tumor
45.2 A 1-week-old infant presents with a right midquadrant abdominal mass and decreased urinary output. There has been no temperature lability, irritability, or abnormal stooling or urine appearance. Which of the following tests would be most helpful in determining the etiology of this infant’s abdominal mass?
A. Complete blood count
B. Abdominal ultrasound
C. Urinary catecholamines
D. Abdominal computed tomography (CT)
E. Barium enema
45.3 A father presents his otherwise healthy 15-month-old daughter to the emergency center with cough, post-tussive emesis, and subjective fever over the past 3 days. He also thinks her abdomen has been hurting her. Diarrhea started yesterday, with “regular” stooling prior to this illness. She has been drinking well and recently had a wet diaper. Physical examination reveals normal vital signs, congested nares, shoddy neck lymphadenopathy, and a mildly distended and apparently tender abdomen without obvious guarding. Which of the following is the next best step in your evaluation?
A. Obtain abdominal computed tomography (CT)
B. Biopsy lymph node
C. Collect 24-hour urine for catecholamines
D. Admit to the hospital for exploratory laparotomy
E. Reassure parent and await spontaneous resolution
45.4 During a routine preventive health visit for a 3-year-old boy, you incidentally note an irregular abdominal mass involving both lower quadrants. His mother denies having noted this previously and declares her son to be generally healthy. There has been neither gastrointestinal distress nor apparent abdominal pain. Beyond the abdominal mass and pallorous conjunctivae, his vital signs and physical examination are normal. Which of the following tests would be most helpful in determining the etiology of his abdominal mass?
A. Abdominal radiograph
B. Chest radiograph
C. Urinary catecholamines
D. Complete blood count
E. Urine myoglobin
45.1 D. The scenario presented is typical for Wilms tumor. Beyond abdominal imaging, checking a urinalysis for hematuria, metabolic panel for renal or hepatic dysfunction, and complete blood count for anemia should be considered in the workup of Wilms tumor.
45.2 B. This infant most likely has a urinary tract obstruction. In the newborn, a palpable abdominal mass is commonly a hydronephrotic or multicystic dys-plastic kidney, and typically can be easily identified by ultrasound.
45.3 E. Upper respiratory tract infection symptoms, neck lymphadenopathy, and diarrhea are consistent with viremia; viral-mediated mesenteric lymph node enlargement can occur and cause nonspecific abdominal pain. Parental reassurance is adequate in this otherwise healthy child with classic viremia signs. An abdominal CT scan may show diffuse, mildly enlarged lymph nodes in mesenteric lymphadenitis, but imaging is rarely warranted unless an etiology for abdominal pain remains elusive.
45.4 C. This boy’s history and examination are consistent with neuroblastoma. Given the vast majority of neuroblastoma patients have elevated urinary catecholamines, a 24-hour quantitative assessment of these metabolites should be confirmatory.
Neuroblastoma may present with an abdominal mass, pallor, proptosis, and “raccoon eyes.”
Masses are often discovered incidentally by a family member or on routine physical examination.
Patients with neuroblastoma are slightly younger and appear sicker than patients with Wilms tumor.
Approximately 90% of neuroblastoma patients have elevated levels of the catecholamine metabolites, vanillylmandelic acid and homovanillic acid.
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